@article {pmid42117483,
year = {2026},
author = {Haq, MM and Benson, C and Kunz, M and Cheung, EYL},
title = {Unraveling myoepithelial cell plasticity in breast cancer: a transcriptomic approach.},
journal = {Journal of histotechnology},
volume = {49},
number = {3},
pages = {162-172},
doi = {10.1080/01478885.2026.2655881},
pmid = {42117483},
issn = {2046-0236},
mesh = {Humans ; Female ; *Breast Neoplasms/pathology/genetics/metabolism ; *Transcriptome/genetics ; *Epithelial Cells/metabolism/pathology ; Gene Expression Regulation, Neoplastic/genetics ; *Cell Plasticity/genetics ; Gene Expression Profiling ; Epithelial-Mesenchymal Transition/genetics ; Periostin ; Extracellular Matrix/metabolism ; },
abstract = {Myoepithelial cells (MECs) are integral to mammary gland physiology, classically serving a structural and tumor-suppressive role. While their function in normal breast tissue and ductal carcinoma in situ is well characterized, their behavior in human invasive breast cancer has not been previously examined. In this study, we performed a comprehensive transcriptomic analysis of MECs isolated from seven archived human breast cancer specimens, directly comparing them with MECs from adjacent normal tissue to define gene expression changes associated with invasive progression. The analysis revealed marked transcriptomic reprogramming across three key domains: extracellular matrix (ECM) interactions, epithelial-mesenchymal transition (EMT), and cellular signaling. Notable findings include stromal remodeling characterized by overexpression of 17 distinct collagen genes; compromise of the basement membrane through upregulation of matrix metalloproteinases (MMPs 2, 9, 11, and 14); and dysregulation of epithelial markers (KRT5, KRT7, KRT14), consistent with a phenotypic shift toward a cancer-associated fibroblast (CAF)-like state. In addition, increased expression of pro-tumorigenic mediators such as SPARC, POSTN, and integrin subunits was observed. Despite the limited sample size, these results indicate substantial molecular plasticity in MECs, suggesting a transition from a tumor-suppressive to a tumor-promoting phenotype during invasive disease. Overall, this study identifies a fundamental shift in myoepithelial identity and provides a critical framework for future investigations into the role of MEC plasticity in driving breast cancer progression.},
}

Humans
Female
*Breast Neoplasms/pathology/genetics/metabolism
*Transcriptome/genetics
*Epithelial Cells/metabolism/pathology
Gene Expression Regulation, Neoplastic/genetics
*Cell Plasticity/genetics
Gene Expression Profiling
Epithelial-Mesenchymal Transition/genetics
Periostin
Extracellular Matrix/metabolism

@article {pmid42166521,
year = {2026},
author = {Tokura, M and Nakayama, J and Suzuki, H and Ochi, M and Umemori, M and Shiino, S and Yoshida, M and Takayama, S and Yatabe, Y and Yamamoto, Y},
title = {Spatial Transcriptomics and Bulk RNA-Seq Analysis Revealed Molecular Classification of Invasive Lobular Carcinoma.},
journal = {Cancer science},
volume = {117},
number = {9},
pages = {2586-2601},
pmid = {42166521},
issn = {1349-7006},
support = {JP256f0137008//Japan Agency for Medical Research and Development/ ; 23K06665//Japan Society for the Promotion of Science/ ; 21H02721//Japan Society for the Promotion of Science/ ; //MSD Life Sciences Foundation, Public Interest Incorporated Foundation/ ; 23812437//New Energy and Industrial Technology Development Organization/ ; //Kanzawa Medical Research Foundation/ ; //Chemo-Sero-Therapeutic Research Institute/ ; //Foundation for Promotion of Cancer Research/ ; //Takeda Science Foundation/ ; //SGH Foundation/ ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/pathology/classification ; *Carcinoma, Lobular/genetics/pathology/classification ; Spatial Transcriptomics ; Prognosis ; Gene Expression Profiling/methods ; RNA-Seq/methods ; Transcriptome ; Gene Expression Regulation, Neoplastic ; Sequence Analysis, RNA ; },
abstract = {Invasive lobular carcinoma (ILC) is a special type of breast cancer. The histological subtypes of ILC exhibit diverse morphological features, and the prognosis differs accordingly. Compared with patients with classic-ILC (C-ILC), patients with pleomorphic-ILC (P-ILC) have a worse prognosis, owing to high-grade nuclear atypia and mitotic cells. However, the molecular differences between C-ILC and P-ILC remain unclear. To address this gap, we performed spatial transcriptomic profiling on four fresh-frozen C-ILC samples and four fresh-frozen P-ILC samples, followed by confirmation of reproducibility in bulk RNA-seq datasets. We identified significant enrichment of cellular response to heat stress in P-ILC. Furthermore, molecular clustering analysis using genes differentially expressed across ILC samples in spatial transcriptome revealed that ILC has three molecular subtypes: proliferative (PR), immunoreactive (IM), and stroma-rich (ST), associated with distinct prognostic outcomes. Although these molecular subtypes did not completely correspond to C-ILC or P-ILC, PR tended to include P-ILC, and ST tended to include C-ILC. These molecular clusters exhibited features comparable to previously reported subtypes. Despite these phenotypic features, ILC is generally treated similarly to invasive ductal carcinoma (IDC), with limited consideration of molecular subtype classification. Our findings suggest that molecular profiling may more accurately reflect prognosis than conventional histological classification and may provide potential diagnostic markers and therapeutic targets.},
}

Humans
Female
*Breast Neoplasms/genetics/pathology/classification
*Carcinoma, Lobular/genetics/pathology/classification
Spatial Transcriptomics
Prognosis
Gene Expression Profiling/methods
RNA-Seq/methods
Transcriptome
Gene Expression Regulation, Neoplastic
Sequence Analysis, RNA

@article {pmid42678278,
year = {2026},
author = {Machado, J and Karthikaisamy, V and Mohr, H and Kaltenecker, D and Benedikt, P and Morigny, P and Mhamane, A and Geppert, J and Fumo, AR and Haase, K and Simoes, E and Lima, JDCC and Georgiadi, A and Krüger, A and Otoch, JP and Martignoni, ME and Baracos, VE and Jamal-Hanjani, M and Seelaender, MCL and Prokopchuk, O and Szendrödi, J and Rohm, M and Herzig, S and Berriel Diaz, M},
title = {Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {OF1-OF25},
doi = {10.1158/2159-8290.CD-26-0045},
pmid = {42678278},
issn = {2159-8290},
support = {329628492//Deutsche Forschungsgemeinschaft (DFG)/ ; EKSE.23//Else Kröner-Fresenius-Stiftung (EKFS)/ ; Horizon 2020 #949017//European Commission (EC)/ ; C11496/A17786//Cancer Research UK (CRUK)/ ; CGCATF-2021/100035//Cancer Research UK (CRUK)/ ; OT2CA278701-01S2//National Cancer Institute (NCI)/ ; //Edith-Haberland-Wagner Foundation/ ; //Helmholtz Research School for Diabetes/ ; //Helmholtz Association - Initiative and Networking Fund/ ; C444/A15953//Cancer Research UK (CRUK)/ ; },
abstract = {UNLABELLED: Cancer cachexia is a devastating wasting syndrome with no approved therapies. In this study, we identify the tumor-derived glycoprotein ADAMTSL4 as a circulating factor associated with body weight loss in preclinical cachexia models and patients with colorectal and lung cancers. In mice, Adamtsl4 overexpression converted non-cachexia-inducing tumors into cachexia-inducing tumors, whereas its deletion in cachexia-inducing tumors spared fat and muscle, blunted muscle atrophy signatures, and reduced cachexia severity. ADAMTSL4 engages the latency-associated peptide (LAP) of TGFβ1, promoting local activation of TGFβ1 at muscle cell membranes. Genetic blockade of proTGFβ1 or pharmacologic inhibition of TGFβ signaling reduced ADAMTSL4-dependent wasting in adipocytes and muscle cells. Suppression of tumor-derived ADAMTSL4 attenuated skeletal muscle fibrosis in mice. Together, the association between increased circulating ADAMTSL4 levels and TGFβ-driven muscle atrophy and fibrosis gene signatures in patients with cachectic cancer identifies ADAMTSL4 as an upstream regulator of TGFβ1 and a potential therapeutic target in cancer cachexia.

SIGNIFICANCE: Cancer cachexia lacks effective therapies and remains a major cause of cancer-related morbidity and mortality. We identify tumor-derived ADAMTSL4 as an upstream regulator of latent TGFβ activation via LAP engagement that promotes multiorgan wasting and fibrosis-related remodeling. Targeting ADAMTSL4 may provide a selective therapeutic strategy without systemic TGFβ pathway blockade.},
}

@article {pmid42668584,
year = {2026},
author = {Zhang, CM and Chau, K and Banerjee, S and Swigris, JJ and Krishnan, JK and Kaner, RJ and Martinez, FJ and Tobin, JN and Safford, MM and Aronson, KI},
title = {Pilot randomized controlled trial of a peer coach-led behavioral and educational intervention to enhance quality of life in patients living with hypersensitivity pneumonitis: Protocol for the RISE-HP study.},
journal = {Contemporary clinical trials communications},
volume = {53},
number = {},
pages = {101678},
pmid = {42668584},
issn = {2451-8654},
abstract = {BACKGROUND: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by an inhalational environmental exposure. Patients living with HP experience significant stress, uncertainty, and hypervigilance about the management of their disease and prognosis. These factors lead to reduced health-related quality of life (HRQOL), an important outcome that no interventions currently target.

OBJECTIVE: The goal of this behavioral and educational intervention, RISE-HP, is to improve HRQOL in people who have HP. The objective of this pilot study is to assess feasibility, acceptability, and preliminary effectiveness of the RISE-HP intervention.

METHODS: This pilot randomized controlled trial will be conducted in patients over the age of 18 with a diagnosis of HP. Forty participants will be randomly assigned to receive either the RISE-HP intervention (meetings with a peer coach focused on living well with their HP using cognitive behavioral techniques and motivational interviewing) or an attention control (general health education sessions with a research assistant) for 10 weeks. Participants will complete four additional study visits (enrollment, 5 weeks, 10 weeks, and 14 weeks after intervention start) for patient reported outcome measure completion. Primary implementation outcomes will be feasibility and acceptability. Secondary patient-centered effectiveness clinical outcomes will be improvement in HRQOL as measured by the Kings Brief Interstitial Lung Disease (KBILD) questionnaire. Additional secondary patient-reported clinical outcomes include fatigue, anxiety, depression, and self-efficacy.

CONCLUSION: Overall, this study addresses an important gap in HP care by targeting HRQOL and offers a novel non-pharmacologic patient-centered approach to therapy in patients with HP.},
}

@article {pmid42667440,
year = {2026},
author = {Khattak, A and Khan, S and Nauman, F and Ali, I},
title = {Association of EBV EBNA1 C-terminal variations with severity of Invasive ductal carcinoma.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {},
pmid = {42667440},
issn = {1573-4978},
mesh = {Humans ; Female ; *Epstein-Barr Virus Nuclear Antigens/genetics/metabolism ; *Breast Neoplasms/genetics/virology/pathology ; *Carcinoma, Ductal, Breast/genetics/virology/pathology ; Polymorphism, Single Nucleotide/genetics ; Middle Aged ; Herpesvirus 4, Human/genetics ; Adult ; Phylogeny ; Epstein-Barr Virus Infections/genetics/virology/complications ; Aged ; Neoplasm Grading ; Mutation ; },
abstract = {BACKGROUND: Breast cancer is a major cause of mortality, and Epstein-Barr virus (EBV) is considered a potential contributor to cancer development. EBV nuclear antigen 1 (EBNA1) plays a vital role in viral persistence. This study aimed to investigate the association among EBNA1 C-terminal variations and severity of invasive ductal carcinoma (IDC).

METHOD: A total of 60 female participants, were included in this study. EBV positive biopsy samples (N = 30) were obtained from the breast cancer patients while 30 healthy females served as control. The C-terminal region of EBNA1 gene was amplified and sequenced. Statistical analysis was carried out using SPSS v25.

RESULT: Among the breast cancer patients, 97% had IDC and 3% had ductal carcinoma in situ. Regarding tumor grade, 3% of the patients had grade I, 63% had grade II and 33% had grade III tumors. The P-Thr (70%) and its co-infection with V-leu (30%) were observed predominantly in patients with higher grade; however, no significant association was observed. A total of 15 consensus single-nucleotide polymorphisms were observed along with six random mutations. No significant association was reported among random SNPs with breast cancer severity. Phylogenetic analysis shows that our sequences of P-Thr exhibited high similarity with reference sequence NC_009334. All control samples were EBV negative.

CONCLUSION: P-Thr was the predominant EBNA1 prototype in study population. However, no significant association was found between EBNA1 variations with breast cancer severity.},
}

Humans
Female
*Epstein-Barr Virus Nuclear Antigens/genetics/metabolism
*Breast Neoplasms/genetics/virology/pathology
*Carcinoma, Ductal, Breast/genetics/virology/pathology
Polymorphism, Single Nucleotide/genetics
Middle Aged
Herpesvirus 4, Human/genetics
Adult
Phylogeny
Epstein-Barr Virus Infections/genetics/virology/complications
Aged
Neoplasm Grading
Mutation

@article {pmid28475000,
year = {2017},
author = {Wang, Y and Shen, H and Yin, Q and Zhang, T and Liu, Z and Zhang, W and Niu, Y},
title = {Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {39},
number = {5},
pages = {1010428317699754},
doi = {10.1177/1010428317699754},
pmid = {28475000},
issn = {1423-0380},
mesh = {Aged ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/*drug therapy/genetics/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Middle Aged ; NIMA-Related Kinases/biosynthesis/*genetics ; Paclitaxel/*administration & dosage ; Xenograft Model Antitumor Assays ; },
abstract = {NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B-) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B- patients and 52.6% in NIMA-related kinase 2B++ patients (p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.},
}

Aged
Animals
Apoptosis/drug effects
Breast Neoplasms/*drug therapy/genetics/pathology
Cell Line, Tumor
Cell Proliferation/drug effects
Drug Resistance, Neoplasm/*genetics
Female
Gene Expression Regulation, Neoplastic/drug effects
Humans
Mice
Middle Aged
NIMA-Related Kinases/biosynthesis/*genetics
Paclitaxel/*administration & dosage
Xenograft Model Antitumor Assays

@article {pmid28480663,
year = {2017},
author = {Lee, SJ and Choi, YY and Kim, C and Chung, MS},
title = {Correlations between Tumor to Background Ratio on Breast-Specific Gamma Imaging and Prognostic Factors in Breast Cancer.},
journal = {Journal of Korean medical science},
volume = {32},
number = {6},
pages = {1031-1037},
pmid = {28480663},
issn = {1598-6357},
mesh = {Adult ; Aged ; Breast/diagnostic imaging ; Breast Neoplasms/*diagnosis/diagnostic imaging/pathology ; Female ; *Gamma Rays ; Humans ; Ki-67 Antigen/genetics/metabolism ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Prognosis ; Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism ; Receptors, Estrogen/genetics/metabolism ; Receptors, Progesterone/genetics/metabolism ; Technetium Tc 99m Sestamibi/chemistry ; },
abstract = {The purpose of this study was to investigate the correlations between tumor-to-background ratio (TBR) obtained from breast-specific gamma imaging (BSGI) and the prognostic factors of breast cancer. Sixty-seven patients with invasive ductal carcinoma who underwent preoperative BSGI were enrolled. The BSGI images were visually scored from 1 to 5 according to a breast imaging reporting and data system (BIRADS). The TBR results obtained from positive BSGI images were compared according to the following prognostic factors: tumor size; axillary lymph node metastasis; nuclear grade (NG); histologic grade (HG); subtype; Ki-67; and the expression profile of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Among 67 images, 60 were classified as a positive finding (sensitivity 89.6%). A higher TBR value was significantly correlated with tumor size ≥ 2 cm (P = 0.001), axillary lymph node metastasis (P = 0.007), high HG (P = 0.029), negative PR status (P = 0.036), and Ki-67 ≥ 14% (P = 0.007). The TBR showed a significant difference between the luminal A and non-luminal A subtypes (P = 0.007). On multivariate analysis, TBR had a high correlation with tumor size ≥ 2 cm, axillary lymph node metastasis, and negative PR status (P = 0.003, 0.048, and 0.030, respectively). A high TBR on BSGI was significantly correlated with poor prognostic factors of breast cancer. Luminal A subtype, a breast cancer subtype with more favorable prognosis, was associated with a low TBR on BSGI.},
}

Adult
Aged
Breast/diagnostic imaging
Breast Neoplasms/*diagnosis/diagnostic imaging/pathology
Female
*Gamma Rays
Humans
Ki-67 Antigen/genetics/metabolism
Lymphatic Metastasis
Middle Aged
Multivariate Analysis
Neoplasm Grading
Prognosis
Erb-b2 Receptor Tyrosine Kinases/genetics/metabolism
Receptors, Estrogen/genetics/metabolism
Receptors, Progesterone/genetics/metabolism
Technetium Tc 99m Sestamibi/chemistry

@article {pmid28481705,
year = {2017},
author = {Poppe, MM and Agarwal, JP},
title = {Breast Reconstruction With Postmastectomy Radiation: Choices and Tradeoffs.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {35},
number = {22},
pages = {2467-2470},
doi = {10.1200/JCO.2017.72.7388},
pmid = {28481705},
issn = {1527-7755},
mesh = {*Breast Implants ; Breast Neoplasms/pathology/*radiotherapy/surgery ; Carcinoma, Ductal, Breast/*radiotherapy/secondary/surgery ; Female ; Humans ; Lymphatic Metastasis ; *Mammaplasty/methods ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*radiotherapy/surgery ; Radiotherapy, Adjuvant ; Rectus Abdominis/transplantation ; *Surgical Flaps ; Transplantation, Autologous ; },
abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old premenopausal woman presented with multifocal cancer in the right breast, with lesions at 1:00 and 4:00, the largest measuring approximately 3 cm on exam, and multiple palpable right axillary lymph nodes. A core biopsy confirmed invasive ductal carcinoma, grade 2 of 3, that was estrogen receptor positive, progesterone receptor positive, and HER2 negative. Fine needle aspiration of a right axillary node confirmed metastatic carcinoma. A positron emission tomography (PET)/ computed tomography done before starting chemotherapy demonstrated an absence of metastatic disease with expected avidity in two separate breast masses and multiple conglomerated 1-2 cm level I and II axillary lymph nodes. She received neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide, followed by paclitaxel, and had a complete clinical response with resolution of the breast and axillary masses on exam. A repeat PET/computed tomography demonstrated reduced size of the breast and axillary disease, and no significant residual PET avidity. Her breast surgeon recommended a right mastectomy with axillary node dissection. As part of her multidisciplinary treatment plan, she consulted with two plastic surgeons to discuss reconstruction options. Plastic Surgeon A advised placement of an implant at the time of mastectomy while Surgeon B contrasted the pros and cons of an autologous transverse rectus abdominis muscle flap reconstruction with an implant based reconstruction. Surgeon B believed that autologous reconstruction would yield the best long-term cosmetic outcome. Before making her surgery decision, the patient consulted with a radiation oncologist to discuss the effect radiation may have on her reconstruction outcome.},
}

*Breast Implants
Breast Neoplasms/pathology/*radiotherapy/surgery
Carcinoma, Ductal, Breast/*radiotherapy/secondary/surgery
Female
Humans
Lymphatic Metastasis
*Mammaplasty/methods
Mastectomy
Middle Aged
Neoplasms, Multiple Primary/pathology/*radiotherapy/surgery
Radiotherapy, Adjuvant
Rectus Abdominis/transplantation
*Surgical Flaps
Transplantation, Autologous

@article {pmid28484924,
year = {2017},
author = {Turner-Ivey, B and Smith, EL and Rutkovsky, AC and Spruill, LS and Mills, JN and Ethier, SP},
title = {Development of mammary hyperplasia, dysplasia, and invasive ductal carcinoma in transgenic mice expressing the 8p11 amplicon oncogene NSD3.},
journal = {Breast cancer research and treatment},
volume = {164},
number = {2},
pages = {349-358},
pmid = {28484924},
issn = {1573-7217},
support = {P30 CA138313/CA/NCI NIH HHS/United States ; R01 CA100724/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Carcinoma, Ductal, Breast/genetics/*pathology ; Cell Transformation, Neoplastic/genetics/*pathology ; Female ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Hyperplasia ; Lactation ; Mammary Neoplasms, Experimental/genetics/*pathology ; Mice ; Mice, Transgenic ; Neoplasm Grading ; Nuclear Proteins/*genetics ; Promoter Regions, Genetic ; },
abstract = {PURPOSE: NSD3 has been implicated as a candidate driver oncogene from the 8p11-p12 locus, and we have previously published evidence for its amplification and overexpression in human breast cancer. This aim of this study was to further characterize the transforming function of NSD3 in vivo.

METHODS: We generated a transgenic mouse model in which NSD3 gene expression was driven by the MMTV promoter and expressed in mammary epithelium of FVB mice. Mammary glands were fixed and whole mounts were stained with carmine to visualize gland structure. Mammary tumors were formalin-fixed, and paraffin embedded (FFPE) tumors were stained with hematoxylin and eosin.

RESULTS: Pups born to transgenic females were significantly underdeveloped compared to pups born to WT females due to a lactation defect in transgenic female mice. Whole mount analysis of the mammary glands of transgenic female mice revealed a profound defect in functional differentiation of mammary gland alveoli that resulted in the lactation defect. We followed parous and virgin NSD3 transgenic and control mice to 50 weeks of age and observed that several NSD3 parous females developed mammary tumors. Whole mount analysis of the mammary glands of tumor-bearing mice revealed numerous areas of mammary hyperplasia and ductal dysplasia. Histological analysis showed that mammary tumors were high-grade ductal carcinomas, and lesions present in other mammary glands exhibited features of alveolar hyperplasia, ductal dysplasia, and carcinoma in situ.

CONCLUSIONS: Our results are consistent with our previous studies and demonstrate that NSD3 is a transforming breast cancer oncogene.},
}

Animals
Carcinoma, Ductal, Breast/genetics/*pathology
Cell Transformation, Neoplastic/genetics/*pathology
Female
Histone-Lysine N-Methyltransferase/*genetics
Humans
Hyperplasia
Lactation
Mammary Neoplasms, Experimental/genetics/*pathology
Mice
Mice, Transgenic
Neoplasm Grading
Nuclear Proteins/*genetics
Promoter Regions, Genetic

@article {pmid28506312,
year = {2017},
author = {Sameni, M and Cavallo-Medved, D and Franco, OE and Chalasani, A and Ji, K and Aggarwal, N and Anbalagan, A and Chen, X and Mattingly, RR and Hayward, SW and Sloane, BF},
title = {Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ.},
journal = {Breast cancer research : BCR},
volume = {19},
number = {1},
pages = {56},
pmid = {28506312},
issn = {1465-542X},
support = {P30 CA022453/CA/NCI NIH HHS/United States ; R01 CA131990/CA/NCI NIH HHS/United States ; R01 DK110314/DK/NIDDK NIH HHS/United States ; U01 CA151924/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/*genetics/pathology ; Cancer-Associated Fibroblasts/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-6/*genetics ; Mice ; Neoplasm Invasiveness/genetics/pathology ; Plasminogen Activator Inhibitor 1/*genetics ; Proteome/genetics ; Receptors, Urokinase Plasminogen Activator/*genetics ; Tissue Array Analysis ; Tumor Microenvironment/genetics ; Urokinase-Type Plasminogen Activator/*genetics ; Xenograft Model Antitumor Assays ; },
abstract = {BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC.

METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression.

RESULTS: Our results show that MEPs suppress tumor formation by DCIS cells in vivo even in the presence of CAFs. In the in vitro MAME model, MEPs reduce the size of 3D DCIS structures and their degradation of extracellular matrix. We further show that the tumor-suppressive effects of MEPs on DCIS are linked to inhibition of urokinase plasminogen activator (uPA)/urokinase plasminogen activator receptor (uPAR)-mediated proteolysis by plasminogen activator inhibitor 1 (PAI-1) and that they can lessen the tumor-promoting effects of CAFs by attenuating interleukin 6 (IL-6) signaling pathways.

CONCLUSIONS: Our studies using MAME are, to our knowledge, the first to demonstrate a divergent interplay between MEPs and CAFs within the DCIS tumor microenvironment. We show that the tumor-suppressive actions of MEPs are mediated by PAI-1, uPA and its receptor, uPAR, and are sustained even in the presence of the CAFs, which themselves enhance DCIS tumorigenesis via IL-6 signaling. Identifying tumor microenvironmental regulators of DCIS progression will be critical for defining a robust and predictive molecular signature for clinical use.},
}

Animals
Breast Neoplasms/*genetics/pathology
Cancer-Associated Fibroblasts/pathology
Carcinoma, Ductal, Breast/*genetics/pathology
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Interleukin-6/*genetics
Mice
Neoplasm Invasiveness/genetics/pathology
Plasminogen Activator Inhibitor 1/*genetics
Proteome/genetics
Receptors, Urokinase Plasminogen Activator/*genetics
Tissue Array Analysis
Tumor Microenvironment/genetics
Urokinase-Type Plasminogen Activator/*genetics
Xenograft Model Antitumor Assays

@article {pmid28511883,
year = {2017},
author = {Chua, MLK and Lo, W and Pintilie, M and Murgic, J and Lalonde, E and Bhandari, V and Mahamud, O and Gopalan, A and Kweldam, CF and van Leenders, GJLH and Verhoef, EI and Hoogland, AM and Livingstone, J and Berlin, A and Dal Pra, A and Meng, A and Zhang, J and Orain, M and Picard, V and Hovington, H and Bergeron, A and Lacombe, L and Fradet, Y and Têtu, B and Reuter, VE and Fleshner, N and Fraser, M and Boutros, PC and van der Kwast, TH and Bristow, RG},
title = {A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies.},
journal = {European urology},
volume = {72},
number = {5},
pages = {665-674},
doi = {10.1016/j.eururo.2017.04.034},
pmid = {28511883},
issn = {1873-7560},
support = {//CIHR/Canada ; },
mesh = {Adenocarcinoma/*genetics/mortality/pathology/therapy ; Biomarkers, Tumor/*genetics ; Disease Progression ; Disease-Free Survival ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; *Genomic Instability ; Humans ; Kaplan-Meier Estimate ; Male ; Neoplasm Invasiveness ; Netherlands ; New York City ; Ontario ; Phenotype ; Proportional Hazards Models ; Prostatic Neoplasms/*genetics/mortality/pathology/therapy ; Quebec ; RNA, Long Noncoding/*genetics ; Risk Factors ; Time Factors ; Transcriptome ; Treatment Outcome ; Tumor Hypoxia ; },
abstract = {BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma.

OBJECTIVE: We investigated for the co-occurrence of "aggression" factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors.

A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Québec-Université Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center). Pathological specimens were centrally reviewed. Gene copy number and expression, and intraprostatic oxygenation were assessed.

IDC/CA was separately assessed for biochemical relapse risk in the Canadian and MSKCC cohorts. Both cohorts were pooled for analyses on metastasis.

RESULTS AND LIMITATION: Presence of IDC/CA independently predicted for increased risks of biochemical relapse (HRCanadian 2.17, p<0.001; HRMSKCC 2.32, p=0.0035) and metastasis (HRpooled 3.31, p<0.001). IDC/CA+ cancers were associated with an increased percentage of genome alteration (PGA [median] 7.2 vs 3.0, p<0.001), and hypoxia (64.0% vs 45.5%, p=0.17). Combinatorial genomic-pathological indices offered the strongest discrimination for metastasis (C-index 0.805 [clinical+IDC/CA+PGA] vs 0.786 [clinical+IDC/CA] vs 0.761 [clinical]). Profiling of mRNA abundance revealed that long noncoding RNA, SChLAP1, was the only gene expressed at >3-fold higher (p<0.0001) in IDC/CA+ than in IDC/CA- tumors, independently corroborated by increased SChLAP1 RNA in situ hybridization signal. Optimal treatment intensification for IDC/CA+ prostate cancer requires prospective testing.

CONCLUSIONS: The poor outcome associated with IDC and CA subpathologies is associated with a constellation of genomic instability, SChLAP1 expression, and hypoxia. We posit a novel concept in IDC/CA+ prostate cancer, "nimbosus" (gathering of stormy clouds, Latin), which manifests as increased metastatic capacity and lethality.

PATIENT SUMMARY: A constellation of unfavorable molecular characteristics co-occur with intraductal and cribriform subpathologies in prostate cancer. Modern imaging for surveillance and treatment intensification trials should be considered in this adverse subgroup.},
}

Adenocarcinoma/*genetics/mortality/pathology/therapy
Biomarkers, Tumor/*genetics
Disease Progression
Disease-Free Survival
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
*Genomic Instability
Humans
Kaplan-Meier Estimate
Male
Neoplasm Invasiveness
Netherlands
New York City
Ontario
Phenotype
Proportional Hazards Models
Prostatic Neoplasms/*genetics/mortality/pathology/therapy
Quebec
RNA, Long Noncoding/*genetics
Risk Factors
Time Factors
Transcriptome
Treatment Outcome
Tumor Hypoxia

@article {pmid28512126,
year = {2017},
author = {Lo, PK and Zhang, Y and Yao, Y and Wolfson, B and Yu, J and Han, SY and Duru, N and Zhou, Q},
title = {Tumor-associated myoepithelial cells promote the invasive progression of ductal carcinoma in situ through activation of TGFβ signaling.},
journal = {The Journal of biological chemistry},
volume = {292},
number = {27},
pages = {11466-11484},
pmid = {28512126},
issn = {1083-351X},
support = {R01 CA157779/CA/NCI NIH HHS/United States ; R01 CA163820/CA/NCI NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 CA154274/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Breast Neoplasms/genetics/*metabolism/pathology ; Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology ; Cell Line, Tumor ; Epithelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Mice ; Mice, Nude ; MicroRNAs/metabolism ; Myeloid Cells/*metabolism/pathology ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Neoplasm Transplantation ; RNA, Neoplasm/metabolism ; *Signal Transduction ; Transforming Growth Factor beta/*metabolism ; },
abstract = {The normal myoepithelium has a tumor-suppressing nature and inhibits the progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC). Conversely, a growing number of studies have shown that tumor-associated myoepithelial cells have a tumor-promoting effect. Moreover, the exact role of tumor-associated myoepithelial cells in the DCIS-to-IDC development remains undefined. To address this, we explored the role of tumor-associated myoepithelial cells in the DCIS-to-IDC progression. We developed a direct coculture system to study the cell-cell interactions between DCIS cells and tumor-associated myoepithelial cells. Coculture studies indicated that tumor-associated myoepithelial cells promoted the invasive progression of a DCIS cell model in vitro, and mechanistic studies revealed that the interaction with DCIS cells stimulated tumor-associated myoepithelial cells to secrete TGFβ1, which subsequently contributed to activating the TGFβ/Smads pathway in DCIS cells. We noted that activation of the TGFβ signaling pathway promoted the epithelial-mesenchymal transition, basal-like phenotypes, stemness, and invasiveness of DCIS cells. Importantly, xenograft studies further demonstrated that tumor-associated myoepithelial cells enhanced the DCIS-to-IDC progression in vivo Furthermore, we found that TGFβ-mediated induction of oncogenic miR-10b-5p expression and down-regulation of RB1CC1, a miR-10b-5p-targeted tumor-suppressor gene, contributed to the invasive progression of DCIS. Our findings provide the first experimental evidence to directly support the paradigm that altered DCIS-associated myoepithelial cells promote the invasive progression of DCIS into IDC via TGFβ signaling activation.},
}

Animals
Breast Neoplasms/genetics/*metabolism/pathology
Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology
Cell Line, Tumor
Epithelial Cells/*metabolism/pathology
Female
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Mice
Mice, Nude
MicroRNAs/metabolism
Myeloid Cells/*metabolism/pathology
Neoplasm Invasiveness
Neoplasm Proteins/*metabolism
Neoplasm Transplantation
RNA, Neoplasm/metabolism
*Signal Transduction
Transforming Growth Factor beta/*metabolism

@article {pmid28531310,
year = {2017},
author = {Lu, XM and Batugedara, G and Lee, M and Prudhomme, J and Bunnik, EM and Le Roch, KG},
title = {Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.},
journal = {Nucleic acids research},
volume = {45},
number = {13},
pages = {7825-7840},
pmid = {28531310},
issn = {1362-4962},
support = {R01 AI106775/AI/NIAID NIH HHS/United States ; S10 OD016290/OD/NIH HHS/United States ; },
mesh = {Animals ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Genes, Protozoan ; Humans ; Malaria, Falciparum/blood/parasitology ; Plasmodium falciparum/*genetics/growth & development/pathogenicity ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/*genetics/metabolism ; Sequence Analysis, RNA ; Transcription, Genetic ; },
abstract = {Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets.},
}

Animals
Epigenesis, Genetic
Gene Expression Profiling
Gene Expression Regulation, Developmental
*Genes, Protozoan
Humans
Malaria, Falciparum/blood/parasitology
Plasmodium falciparum/*genetics/growth & development/pathogenicity
Promoter Regions, Genetic
RNA Polymerase II/metabolism
RNA, Messenger/genetics/metabolism
RNA, Protozoan/*genetics/metabolism
Sequence Analysis, RNA
Transcription, Genetic

@article {pmid28541858,
year = {2017},
author = {Jean-Louis, CJ and Masdon, J and Smith, B and Battles, O and Dale, P},
title = {The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.},
journal = {The American surgeon},
volume = {83},
number = {5},
pages = {482-485},
pmid = {28541858},
issn = {1555-9823},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Carcinoma In Situ/*epidemiology/pathology/therapy ; Breast Neoplasms/*epidemiology/*pathology/therapy ; Carcinoma, Lobular/*epidemiology/pathology/therapy ; Female ; Humans ; Incidence ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Neoplasms, Multiple Primary/*epidemiology/pathology/therapy ; Retrospective Studies ; Risk Factors ; },
abstract = {For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.},
}

Adult
Aged
Aged, 80 and over
Breast Carcinoma In Situ/*epidemiology/pathology/therapy
Breast Neoplasms/*epidemiology/*pathology/therapy
Carcinoma, Lobular/*epidemiology/pathology/therapy
Female
Humans
Incidence
Mastectomy
Middle Aged
Neoplasm Invasiveness
Neoplasms, Multiple Primary/*epidemiology/pathology/therapy
Retrospective Studies
Risk Factors

@article {pmid28543784,
year = {2017},
author = {Chaudhuri, RK and Bojanowski, K},
title = {Improvement of hydration and epidermal barrier function in human skin by a novel compound isosorbide dicaprylate.},
journal = {International journal of cosmetic science},
volume = {39},
number = {5},
pages = {518-526},
doi = {10.1111/ics.12405},
pmid = {28543784},
issn = {1468-2494},
mesh = {Administration, Topical ; Aquaporin 3/metabolism ; Body Water ; Cadherins/genetics ; Caprylates/administration & dosage/*pharmacology ; Cell Differentiation/drug effects ; Emollients/administration & dosage ; Epidermis/*drug effects/metabolism ; Glycerol/administration & dosage ; Humans ; Hyaluronan Receptors/metabolism ; Keratinocytes/cytology/drug effects ; Oligonucleotide Array Sequence Analysis ; Placebos ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; Up-Regulation/drug effects ; Water/metabolism ; },
abstract = {OBJECTIVE: The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin.

METHODS: The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo.

RESULTS: IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin.

CONCLUSION: Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing.},
}

Administration, Topical
Aquaporin 3/metabolism
Body Water
Cadherins/genetics
Caprylates/administration & dosage/*pharmacology
Cell Differentiation/drug effects
Emollients/administration & dosage
Epidermis/*drug effects/metabolism
Glycerol/administration & dosage
Humans
Hyaluronan Receptors/metabolism
Keratinocytes/cytology/drug effects
Oligonucleotide Array Sequence Analysis
Placebos
Polymerase Chain Reaction
RNA, Messenger/genetics
Up-Regulation/drug effects
Water/metabolism

@article {pmid28560596,
year = {2017},
author = {Petruolo, OA and Pilewskie, M and Patil, S and Barrio, AV and Stempel, M and Wen, HY and Morrow, M},
title = {Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy.},
journal = {Annals of surgical oncology},
volume = {24},
number = {9},
pages = {2556-2562},
pmid = {28560596},
issn = {1534-4681},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Axilla ; Breast Neoplasms/*drug therapy/metabolism/*pathology/surgery ; Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary/surgery ; Carcinoma, Lobular/*drug therapy/metabolism/secondary/surgery ; Chemotherapy, Adjuvant ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Mastectomy, Segmental ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Retrospective Studies ; },
abstract = {BACKGROUND: The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR).

OBJECTIVE: The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC.

METHODS: Patients with stage I-III ER+, HER2- breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP).

RESULTS: From 2007 to 2016, 402 ER+/HER2- cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II-III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p < 0.0001). Patients with ILC initially ineligible for BCS (n = 56) were less likely to downstage than those with invasive ductal carcinoma (IDC; n = 183, 16 vs. 48%, p ≤ 0.0001), with a similar trend in the axilla (p = 0.086). The rates of BCS eligibility after NAC were highest in PR-/HP patients (62%) and lowest in PR+/non-HP patients (29%) [p = 0.005]. In the axilla, nodal pCR among cN+ patients (n = 301) ranged from 0 to 35% (p < 0.0001) within these groups, and was most frequent in PR-/HP patients.

CONCLUSIONS: ER+/HER2- patients most likely to benefit from NAC are those with PR- and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.},
}

Adult
Aged
Axilla
Breast Neoplasms/*drug therapy/metabolism/*pathology/surgery
Carcinoma, Ductal, Breast/*drug therapy/metabolism/secondary/surgery
Carcinoma, Lobular/*drug therapy/metabolism/secondary/surgery
Chemotherapy, Adjuvant
Humans
Lymph Nodes/pathology
Lymphatic Metastasis
Mastectomy, Segmental
Middle Aged
Neoadjuvant Therapy
Neoplasm Grading
Neoplasm Staging
Erb-b2 Receptor Tyrosine Kinases/metabolism
Receptors, Estrogen/metabolism
Receptors, Progesterone/metabolism
Retrospective Studies

@article {pmid28561207,
year = {2017},
author = {Rice, GI and Kitabayashi, N and Barth, M and Briggs, TA and Burton, ACE and Carpanelli, ML and Cerisola, AM and Colson, C and Dale, RC and Danti, FR and Darin, N and De Azua, B and De Giorgis, V and De Goede, CGL and Desguerre, I and De Laet, C and Eslahi, A and Fahey, MC and Fallon, P and Fay, A and Fazzi, E and Gorman, MP and Gowrinathan, NR and Hully, M and Kurian, MA and Leboucq, N and Lin, JS and Lines, MA and Mar, SS and Maroofian, R and Martí-Sanchez, L and McCullagh, G and Mojarrad, M and Narayanan, V and Orcesi, S and Ortigoza-Escobar, JD and Pérez-Dueñas, B and Petit, F and Ramsey, KM and Rasmussen, M and Rivier, F and Rodríguez-Pombo, P and Roubertie, A and Stödberg, TI and Toosi, MB and Toutain, A and Uettwiller, F and Ulrick, N and Vanderver, A and Waldman, A and Livingston, JH and Crow, YJ},
title = {Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.},
journal = {Neuropediatrics},
volume = {48},
number = {3},
pages = {166-184},
pmid = {28561207},
issn = {1439-1899},
support = {309449/ERC_/European Research Council/International ; K12 NS001692/NS/NINDS NIH HHS/United States ; MR/M501803/1/MRC_/Medical Research Council/United Kingdom ; TRF-2016-09-002/DH_/Department of Health/United Kingdom ; },
mesh = {Adenosine Deaminase/*genetics ; Adolescent ; Adult ; Autoimmune Diseases of the Nervous System/diagnostic imaging/*genetics/*immunology ; Biomarkers/metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interferon Type I/*metabolism ; Male ; Mutation ; Nervous System Malformations/diagnostic imaging/*genetics/*immunology ; Phenotype ; RNA-Binding Proteins/*genetics ; Young Adult ; },
abstract = {We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.},
}

Adenosine Deaminase/*genetics
Adolescent
Adult
Autoimmune Diseases of the Nervous System/diagnostic imaging/*genetics/*immunology
Biomarkers/metabolism
Child
Child, Preschool
Female
Humans
Infant
Interferon Type I/*metabolism
Male
Mutation
Nervous System Malformations/diagnostic imaging/*genetics/*immunology
Phenotype
RNA-Binding Proteins/*genetics
Young Adult

@article {pmid28567637,
year = {2017},
author = {Lambein, K and Van Bockstal, M and Vandemaele, L and Van den Broecke, R and Cocquyt, V and Geenen, S and Denys, H and Libbrecht, L},
title = {Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {471},
number = {5},
pages = {575-587},
pmid = {28567637},
issn = {1432-2307},
mesh = {Adult ; Aged ; Biomarkers, Tumor/analysis/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology ; Disease Progression ; Female ; Gene Amplification ; Humans ; Middle Aged ; Erb-b2 Receptor Tyrosine Kinases/*genetics ; },
abstract = {Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.},
}

Adult
Aged
Biomarkers, Tumor/analysis/*genetics
Breast Neoplasms/*genetics/pathology
Carcinoma, Ductal, Breast/*genetics/pathology
Carcinoma, Intraductal, Noninfiltrating/*genetics/pathology
Disease Progression
Female
Gene Amplification
Humans
Middle Aged
Erb-b2 Receptor Tyrosine Kinases/*genetics

@article {pmid28591263,
year = {2017},
author = {Rodrigues, FT and Klemig, LR and Cardozo, MRP and Alves, PC and Aguiar, VM and Lessa, CS},
title = {Myiasis associated with an invasive ductal carcinoma of the left breast: case study.},
journal = {Revista do Instituto de Medicina Tropical de Sao Paulo},
volume = {59},
number = {},
pages = {e35},
pmid = {28591263},
issn = {1678-9946},
mesh = {Adult ; Animals ; Antiparasitic Agents/therapeutic use ; Breast Neoplasms/*complications/parasitology ; Carcinoma, Ductal/*complications/parasitology ; Female ; Humans ; Ivermectin/therapeutic use ; Larva ; Myiasis/*complications/diagnosis/drug therapy ; },
abstract = {Most breast cancers originate in the ductal epithelium and are referred to as invasive ductal carcinoma. In this study we report on the clinical procedures adopted to diagnose myiasis in association with infiltrating metastatic breast carcinoma in a female patient. A 41 years old woman came to the Federal Hospital of Andaraí complaining of intense itching, warmth, redness and hardening of the breast, which had acquired the aspect of an orange peel. A lesion in the left breast was cavitated, dimpled, had fetid odor, and had fibrotic and infected air nodules filled with exudate and Dipteran larvae. The tissue was cleaned and 33 larvae were extracted. The patient was hospitalized and received Ivermectin. Eighteen of the larvae extracted from the patient were placed in 70% alcohol, and twelve were placed in a container with sterile wood shavings under controlled conditions until they metamorphosed into adults. The taxonomic identification of the flies revealed that the culprit was Cochliomyia hominivorax. A histopathological exam conducted three months earlier had revealed infiltrating ductal carcinoma. Two months after the myiasis treatment, the breast tissue had healed. The patient had waited ten days from the onset of the myiasis to seek treatment, and that delay interfered negatively in the prognosis of both the neoplasm and the myiasis. This study is relevant to public health in view of the strong social impact of myiasis.},
}

Adult
Animals
Antiparasitic Agents/therapeutic use
Breast Neoplasms/*complications/parasitology
Carcinoma, Ductal/*complications/parasitology
Female
Humans
Ivermectin/therapeutic use
Larva
Myiasis/*complications/diagnosis/drug therapy

@article {pmid28592128,
year = {2017},
author = {Li, J and Zhang, X and Zheng, L and Liu, Y},
title = {Association of nuclear FOXP3 expression with low Ki67 index and better prognosis in patients with breast invasive ductal carcinoma.},
journal = {Neoplasma},
volume = {64},
number = {5},
pages = {754-761},
doi = {10.4149/neo_2017_514},
pmid = {28592128},
issn = {0028-2685},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/diagnosis/*genetics ; Carcinoma, Ductal, Breast/diagnosis/*genetics ; Female ; Forkhead Transcription Factors/genetics/*metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/*metabolism ; Prognosis ; },
abstract = {Recent studies have provided clear evidence that some types of human cancer cells expressed Forkhead Box Protein 3 (FOXP3). However, the presence and role of FOXP3 in breast cancer are still contradictory up to now. In this study, we detected the expression of FOXP3 protein by immunohistochemistry in 123 cases of breast invasive ductal carcinoma. It exhibited that the subcellular localization of FOXP3 expression in breast cancer cells is heterogeneous. In nucleus, FOXP3 expression ratio was 47.97% (59/123) and the nuclear FOXP3 expression was significantly associated with lower Ki67 index (P=0.041), negative vessel tumor embolus (P=0.024). It was also significantly correlated with the molecular subtypes of breast cancer (P=0.002), displaying the highest ratio in the Luminal A subtype (68.18%). Kaplan-Meier analysis indicated that high nuclear FOXP3 expression was associated with better overall survival (OS) (94.92% vs. 82.81%, P=0.022) and disease-free survival (DFS) (91.53% vs. 76.56%, P=0.026). Moreover, nuclear FOXP3 represented an independent prognostic factor for OS (P =0.033) in multivariate analysis. However, in cytoplasm, FOXP3 expression ratio was 63.41% (78/123) and no statistic prognostic significance was found. Thus, our data demonstrated that nuclear FOXP3 expression correlated with low Ki-67 index and better outcome in breast invasive ductal carcinoma, indicating that FOXP3 acted as a potential prognostic marker for breast cancer.},
}

Biomarkers, Tumor
Breast Neoplasms/diagnosis/*genetics
Carcinoma, Ductal, Breast/diagnosis/*genetics
Female
Forkhead Transcription Factors/genetics/*metabolism
Humans
Kaplan-Meier Estimate
Ki-67 Antigen/*metabolism
Prognosis

@article {pmid28618949,
year = {2017},
author = {Zhao, HY and Han, Y and Wang, J and Yang, LH and Zheng, XY and Du, J and Wu, GP and Wang, EH},
title = {IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {39},
number = {6},
pages = {1010428317705769},
doi = {10.1177/1010428317705769},
pmid = {28618949},
issn = {1423-0380},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology/surgery ; Carcinoma, Ductal/*genetics/pathology/surgery ; Cyclin D1/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Prognosis ; Proto-Oncogene Proteins c-myc/genetics ; Survival Analysis ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; ras GTPase-Activating Proteins/*genetics ; },
abstract = {IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.},
}

Adult
Aged
Biomarkers, Tumor/*genetics
Breast Neoplasms/*genetics/pathology/surgery
Carcinoma, Ductal/*genetics/pathology/surgery
Cyclin D1/genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Middle Aged
Neoplasm Invasiveness/genetics
Prognosis
Proto-Oncogene Proteins c-myc/genetics
Survival Analysis
Wnt Signaling Pathway/genetics
beta Catenin/genetics
ras GTPase-Activating Proteins/*genetics

@article {pmid28625415,
year = {2018},
author = {de Zárraga Mata, C and Thomas Salom, G and Vilella Martorell, A and Salvà Ramonell, F and Maura Oliver, ÁL and Dolz Abadía, C},
title = {Gastric metastatic extension of invasive ductal carcinoma of the breast with atypical endoscopic presentation.},
journal = {Gastroenterologia y hepatologia},
volume = {41},
number = {5},
pages = {304-305},
doi = {10.1016/j.gastrohep.2017.04.006},
pmid = {28625415},
issn = {0210-5705},
mesh = {Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/therapy ; Chemoradiotherapy ; Combined Modality Therapy ; Fatal Outcome ; Female ; *Gastroscopy ; Humans ; Image-Guided Biopsy ; Incidental Findings ; Lymphatic Metastasis ; Mastectomy, Segmental ; Stomach Neoplasms/*diagnostic imaging/therapy ; },
}

Adult
Aged
Biopsy, Fine-Needle
Breast Neoplasms/*pathology/therapy
Carcinoma, Ductal, Breast/diagnostic imaging/*secondary/therapy
Chemoradiotherapy
Combined Modality Therapy
Fatal Outcome
Female
*Gastroscopy
Humans
Image-Guided Biopsy
Incidental Findings
Lymphatic Metastasis
Mastectomy, Segmental
Stomach Neoplasms/*diagnostic imaging/therapy

@article {pmid28628772,
year = {2017},
author = {Carbognin, L and Sperduti, I and Fabi, A and Dieci, MV and Kadrija, D and Griguolo, G and Pilotto, S and Guarneri, V and Zampiva, I and Brunelli, M and Orvieto, E and Nortilli, R and Fiorio, E and Parolin, V and Manfrin, E and Caliò, A and Nisticò, C and Pellini, F and Scarpa, A and Pollini, GP and Conte, P and Tortora, G and Bria, E},
title = {Prognostic impact of proliferation for resected early stage 'pure' invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation.},
journal = {Breast (Edinburgh, Scotland)},
volume = {35},
number = {},
pages = {21-26},
doi = {10.1016/j.breast.2017.06.005},
pmid = {28628772},
issn = {1532-3080},
mesh = {Adult ; Aged ; Breast Neoplasms/*immunology/*pathology ; Carcinoma, Lobular/*immunology/*pathology ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis ; },
abstract = {INTRODUCTION: The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC).

METHODS: Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well.

RESULTS: Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap.

CONCLUSIONS: Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.},
}

Adult
Aged
Breast Neoplasms/*immunology/*pathology
Carcinoma, Lobular/*immunology/*pathology
Female
Humans
Ki-67 Antigen/*metabolism
Middle Aged
Neoplasm Staging
Prognosis
Retrospective Studies
Survival Analysis

@article {pmid28633434,
year = {2017},
author = {Singh, DK and Gholamalamdari, O and Jadaliha, M and Ling Li, X and Lin, YC and Zhang, Y and Guang, S and Hashemikhabir, S and Tiwari, S and Zhu, YJ and Khan, A and Thomas, A and Chakraborty, A and Macias, V and Balla, AK and Bhargava, R and Janga, SC and Ma, J and Prasanth, SG and Lal, A and Prasanth, KV},
title = {PSIP1/p75 promotes tumorigenicity in breast cancer cells by promoting the transcription of cell cycle genes.},
journal = {Carcinogenesis},
volume = {38},
number = {10},
pages = {966-975},
pmid = {28633434},
issn = {1460-2180},
support = {R01 GM088252/GM/NIGMS NIH HHS/United States ; R01 GM099669/GM/NIGMS NIH HHS/United States ; R01 GM123314/GM/NIGMS NIH HHS/United States ; R01 HG007352/HG/NHGRI NIH HHS/United States ; },
mesh = {Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Breast Neoplasms/*genetics/mortality/*pathology ; Cell Cycle/*genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Chromatin/genetics/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Oncogenes ; Promoter Regions, Genetic ; RNA Polymerase II/genetics/metabolism ; Tissue Array Analysis ; Transcription Factors/*genetics/metabolism ; Triple Negative Breast Neoplasms/genetics/pathology ; },
abstract = {Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in BC initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in BC progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma. Survival data analyses revealed that the levels of PSIP1 showed a negative association with TNBC patient survival. Depletion of PSIP1/p75 significantly reduced the tumorigenicity and metastatic properties of TNBC cell lines while its over-expression promoted tumorigenicity. Further, gene expression studies revealed that PSIP1 regulates the expression of genes controlling cell-cycle progression, cell migration and invasion. Finally, by interacting with RNA polymerase II, PSIP1/p75 facilitates the association of RNA pol II to the promoter of cell cycle genes and thereby regulates their transcription. Our findings demonstrate an important role of PSIP1/p75 in TNBC tumorigenicity by promoting the expression of genes that control the cell cycle and tumor metastasis.},
}

Adaptor Proteins, Signal Transducing/*genetics/metabolism
Breast Neoplasms/*genetics/mortality/*pathology
Cell Cycle/*genetics
Cell Line, Tumor
Cell Proliferation/genetics
Chromatin/genetics/metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
Oncogenes
Promoter Regions, Genetic
RNA Polymerase II/genetics/metabolism
Tissue Array Analysis
Transcription Factors/*genetics/metabolism
Triple Negative Breast Neoplasms/genetics/pathology

@article {pmid28647915,
year = {2017},
author = {Kizy, S and Huang, JL and Marmor, S and Tuttle, TM and Hui, JYC},
title = {Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast.},
journal = {Breast cancer research and treatment},
volume = {165},
number = {3},
pages = {757-763},
doi = {10.1007/s10549-017-4355-9},
pmid = {28647915},
issn = {1573-7217},
mesh = {Adolescent ; Adult ; Aged ; *Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Lobular/*genetics/*mortality/pathology ; Female ; *Gene Expression Profiling ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Young Adult ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) of the breast has unique clinicopathologic characteristics, compared to invasive ductal carcinoma. The role of the 21-gene Recurrence Score (RS) has not been clearly defined for ILC. We sought to determine the prognostic value of RS and the impact of adjuvant chemotherapy on long-term survival in patients with ILC.

METHODS: Utilizing the Surveillance, Epidemiology and End Results database from 2004 to 2013, we identified records of women aged 18-74 years, diagnosed with estrogen receptor (ER)-positive ILC (stage I to III) with RS available. We categorized patients into risk groups based on the traditional RS cutoffs and into those of the Trial Assigning Individualized Options for Treatment (TAILORx). Five-year breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and Cox proportional hazards models.

RESULTS: Of the 7316 women included, 21% were in the low-risk; 71%, intermediate-risk; and 8%, high-risk groups as per TAILORx RS cutoffs. The 5-year BCSS was 99% in the low-risk, 99% in the intermediate-risk, and 96% in the high-risk groups. A high-risk RS as per TAILORx cutoff was independently associated with increased mortality (hazard ratio [HR] of death 2.37, 95% confidence interval [CI] 1.14-4.95) when compared to a low-risk RS. In both the high-risk and intermediate-risk groups, adjuvant chemotherapy was not significantly associated with the HR of death (high-risk, HR 1.14, 95% CI 0.55-2.38; intermediate-risk, HR 1.08, 95% CI 0.62-1.87).

CONCLUSION: For patients with ER-positive ILC, 8% were in the high-risk and 72% were in the intermediate-risk groups as per the TAILORx RS cutoffs. In the high-risk group, the RS predicted a lower 5-year BCSS. Adjuvant chemotherapy did not seem to confer a survival benefit for either the intermediate- or the high-risk cohorts.},
}

Adolescent
Adult
Aged
*Biomarkers, Tumor
Breast Neoplasms/*genetics/*mortality/pathology
Carcinoma, Lobular/*genetics/*mortality/pathology
Female
*Gene Expression Profiling
Humans
Kaplan-Meier Estimate
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Proportional Hazards Models
Risk Factors
Young Adult

@article {pmid28652380,
year = {2017},
author = {Gil Del Alcazar, CR and Huh, SJ and Ekram, MB and Trinh, A and Liu, LL and Beca, F and Zi, X and Kwak, M and Bergholtz, H and Su, Y and Ding, L and Russnes, HG and Richardson, AL and Babski, K and Min Hui Kim, E and McDonnell, CH and Wagner, J and Rowberry, R and Freeman, GJ and Dillon, D and Sorlie, T and Coussens, LM and Garber, JE and Fan, R and Bobolis, K and Allred, DC and Jeong, J and Park, SY and Michor, F and Polyak, K},
title = {Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.},
journal = {Cancer discovery},
volume = {7},
number = {10},
pages = {1098-1115},
pmid = {28652380},
issn = {2159-8290},
support = {F32 CA156991/CA/NCI NIH HHS/United States ; R35 CA197623/CA/NCI NIH HHS/United States ; U54 CA193461/CA/NCI NIH HHS/United States ; },
mesh = {B7-H1 Antigen/genetics ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*immunology ; CD3 Complex/genetics ; Carcinoma, Ductal, Breast/genetics/*immunology ; Carcinoma, Intraductal, Noninfiltrating/genetics/*immunology ; Disease Progression ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Leukocyte Common Antigens/genetics ; Erb-b2 Receptor Tyrosine Kinases/genetics ; T-Lymphocytes/*immunology ; Tumor Microenvironment ; },
abstract = {To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45[+]CD3[+] T cells demonstrated a decrease in CD8[+] signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB[+]CD8[+] T cells in IDC than in DCIS, including in matched DCIS and recurrent IDC. T-cell receptor clonotype diversity was significantly higher in DCIS than in IDCs. Immune checkpoint protein TIGIT-expressing T cells were more frequent in DCIS, whereas high PD-L1 expression and amplification of CD274 (encoding PD-L1) was only detected in triple-negative IDCs. Coamplification of a 17q12 chemokine cluster with ERBB2 subdivided HER2[+] breast tumors into immunologically and clinically distinct subtypes. Our results show coevolution of cancer cells and the immune microenvironment during tumor progression.Significance: The design of effective cancer immunotherapies requires the understanding of mechanisms underlying immune escape during tumor progression. Here we demonstrate a switch to a less active tumor immune environment during the in situ to invasive breast carcinoma transition, and identify immune regulators and genomic alterations that shape tumor evolution. Cancer Discov; 7(10); 1098-115. ©2017 AACR.See related commentary by Speiser and Verdeil, p. 1062This article is highlighted in the In This Issue feature, p. 1047.},
}

B7-H1 Antigen/genetics
Biomarkers, Tumor/genetics
Breast Neoplasms/genetics/*immunology
CD3 Complex/genetics
Carcinoma, Ductal, Breast/genetics/*immunology
Carcinoma, Intraductal, Noninfiltrating/genetics/*immunology
Disease Progression
Female
Gene Expression Profiling/*methods
Gene Expression Regulation, Neoplastic
Humans
Leukocyte Common Antigens/genetics
Erb-b2 Receptor Tyrosine Kinases/genetics
T-Lymphocytes/*immunology
Tumor Microenvironment

@article {pmid28658335,
year = {2017},
author = {Aquino, RGF and Vasques, PHD and Cavalcante, DIM and Oliveira, ALS and Oliveira, BMK and Pinheiro, LGP},
title = {Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases.},
journal = {Revista do Colegio Brasileiro de Cirurgioes},
volume = {44},
number = {2},
pages = {163-170},
doi = {10.1590/0100-69912017002010},
pmid = {28658335},
issn = {1809-4546},
mesh = {Adult ; Aged ; Aged, 80 and over ; *Axilla ; Breast Neoplasms/*pathology ; Carcinoma, Ductal/*pathology/*secondary ; Cross-Sectional Studies ; Female ; Humans ; Middle Aged ; Neoplasm Invasiveness ; },
abstract = {OBJECTIVE: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma.

METHODS: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases.

RESULTS: the mean patients'age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001).

CONCLUSION: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases.},
}

Adult
Aged
Aged, 80 and over
*Axilla
Breast Neoplasms/*pathology
Carcinoma, Ductal/*pathology/*secondary
Cross-Sectional Studies
Female
Humans
Middle Aged
Neoplasm Invasiveness

@article {pmid28661760,
year = {2017},
author = {Curigliano, G and Criscitiello, C},
title = {Maximizing the Clinical Benefit of Anthracyclines in Addition to Taxanes in the Adjuvant Treatment of Early Breast Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {35},
number = {23},
pages = {2600-2603},
doi = {10.1200/JCO.2017.72.5960},
pmid = {28661760},
issn = {1527-7755},
mesh = {Anthracyclines/administration & dosage/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Breast Neoplasms/pathology/*therapy ; Bridged-Ring Compounds/administration & dosage ; Carcinoma, Ductal, Breast/secondary/*therapy ; Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; *Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Invasiveness ; Radiotherapy, Adjuvant ; Taxoids/administration & dosage ; },
abstract = {The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A healthy 56-year-old postmenopausal woman discovered a palpable mass at the one o'clock position of the left breast. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer that measured 3.5 cm. There was extensive lymphovascular invasion. Pathology review indicated a poorly differentiated, grade 3 invasive ductal carcinoma and ductal carcinoma in situ (largest focus, 3.5 cm). The margins were negative. Two of the 11 axillary lymph nodes contained metastatic carcinoma. Immunohistochemical studies previously obtained on the core biopsy indicated that the tumor was positive for estrogen receptor expression (50%), negative for progesterone receptor expression, and had a Ki-67 score of 60%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. Our multidisciplinary tumor board recommended adjuvant chemotherapy, postmastectomy radiation therapy, and endocrine therapy. A 52-year-old postmenopausal woman presented with a palpable mass of the right breast. An initial core biopsy confirmed carcinoma in the breast. She underwent quadrantectomy and axillary node dissection. The final pathology report disclosed a moderately differentiated invasive ductal carcinoma (diameter, 2.5 cm). The margins were negative. None of the three sentinel lymph nodes contained metastatic carcinoma. Immunohistochemical studies showed that the tumor was positive for estrogen receptor expression (90%) and for progesterone receptor expression (40%) and had a Ki-67 score of 20%. There was no amplification of the human epidermal growth factor receptor 2/ neu gene. Staging scans were negative for metastatic disease. A genomic assay was obtained and suggested an intermediate to high risk of recurrence. Her past medical history was notable for hypertension and moderately overweight status (body mass index, 39 kg/m[2]). Our multidisciplinary tumor board recommended adjuvant chemotherapy, postsurgical radiation therapy, and endocrine therapy.},
}

Anthracyclines/administration & dosage/adverse effects
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Axilla
Breast Neoplasms/pathology/*therapy
Bridged-Ring Compounds/administration & dosage
Carcinoma, Ductal, Breast/secondary/*therapy
Carcinoma, Intraductal, Noninfiltrating/*drug therapy/pathology/surgery
Chemotherapy, Adjuvant
Female
Humans
*Lymph Node Excision
Lymphatic Metastasis
Mastectomy
Middle Aged
Neoplasm Invasiveness
Radiotherapy, Adjuvant
Taxoids/administration & dosage

@article {pmid28671041,
year = {2017},
author = {Liu, B and Xiong, J and Liu, G and Wu, J and Wen, L and Zhang, Q and Zhang, C},
title = {High expression of Rac1 is correlated with partial reversed cell polarity and poor prognosis in invasive ductal carcinoma of the breast.},
journal = {Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine},
volume = {39},
number = {7},
pages = {1010428317710908},
doi = {10.1177/1010428317710908},
pmid = {28671041},
issn = {1423-0380},
mesh = {Adult ; Aged ; Biomarkers, Tumor/*biosynthesis/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Cell Polarity ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; *Prognosis ; rac1 GTP-Binding Protein/*biosynthesis/genetics ; },
abstract = {The change of cell polarity is usually associated with invasion and metastasis. Partial reverse cell polarity in IDC-NOS may play a role in lymphatic tumor spread. Rac1 is a kind of polarity related protein. It plays an important role in invasion and metastasis in tumors. We here investigated the expression of Rac1 and partial reverse cell polarity status in breast cancer and evaluated their value for prognosis in breast cancer. The association of the expression of Rac1 and MUC-1 with clinicopathological parameters and prognostic significance was evaluated in 162 cases of IDC-NOS paraffin-embedded tissues by immunohistochemical method. The Rac1 messenger RNA expression was measured by real-time polymerase chain reaction in 30 breast cancer patients, which was divided into two groups of partial reverse cell polarity and no partial reverse cell polarity. We found that lymph node metastasis of partial reverse cell polarity patients was higher than no partial reverse cell polarity patients (Z = -4.030, p = 0.000). Rac1 was upregulated in partial reverse cell polarity group than no partial reverse cell polarity group (Z = -3.164, p = 0.002), and there was correlationship between the expression of Rac1 and partial reverse cell polarity status (rs = 0.249, p = 0.001). The level of Rac1 messenger RNA expression in partial reverse cell polarity group was significantly higher compared to no partial reverse cell polarity group (t = -2.527, p = 0.017). Overexpression of Rac1 and partial reverse cell polarity correlates with poor prognosis of IDC-NOS patients (p = 0.011). Partial reverse cell polarity and lymph node metastasis remained as independent predictors for poor disease-free survival of IDC-NOS (p = 0.023, p = 0.046). Our study suggests that partial reverse cell polarity may lead to poor prognosis of breast cancer. Overexpression of Rac1 may lead to polarity change in IDC-NOS of the breast. Therefore, Rac1 could be a therapeutic target for breast cancer.},
}

Adult
Aged
Biomarkers, Tumor/*biosynthesis/genetics
Carcinoma, Ductal, Breast/*genetics/pathology
Cell Polarity
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Middle Aged
Neoplasm Invasiveness/genetics
Neoplasm Staging
*Prognosis
rac1 GTP-Binding Protein/*biosynthesis/genetics

@article {pmid28681371,
year = {2017},
author = {Kumaki, N and Okamatsu, C and Tokuda, Y and Nakamura, N},
title = {Breast Cancer in Patients of Rheumatoid Arthritis with Methotrexate Therapy Mimicking Histopathological Changes after Neoadjuvant Chemotherapy.},
journal = {The Tokai journal of experimental and clinical medicine},
volume = {42},
number = {2},
pages = {104-108},
pmid = {28681371},
issn = {2185-2243},
mesh = {Aged ; Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy ; Breast/*pathology ; Breast Neoplasms/complications/*pathology/*therapy ; Carcinoma, Intraductal, Noninfiltrating/complications/*pathology/*therapy ; *Chemotherapy, Adjuvant ; Female ; Humans ; Lymph Nodes/pathology ; Mastectomy ; Methotrexate/*therapeutic use ; Middle Aged ; *Neoadjuvant Therapy ; },
abstract = {Two breast cancer patients with a history of treatment for long-term rheumatoid arthritis (RA) had histological findings similar to histological changes seen in resected mammary gland specimens following neoadjuvant chemotherapy (NAC). The first patient was a 64-year-old woman who visited our hospital after feeling a lump in her left breast. The second patient was a 68-year-old woman who visited our hospital for an indentation in her left nipple. They were diagnosed with breast cancer following detailed examinations and underwent mastectomy. Both patients had a history of RA and were being treated with Methotrexate. The histological diagnoses of these patients were invasive ductal carcinoma, but frequent dispersal of cancer cell nests, stromal fibrosis, elastosis, edema and inflammatory cell infiltration were seen. Fibrosis was also found in the dissected lymph node. These histological findings were extremely similar to changes that occur in the mammary gland tissue after NAC; however, these patients had not undergone NAC. Methotrexate, which was being administered as an anti-rheumatic drug to the two patients, might have played a role similar to that of metronomic chemotherapy, which involves the continuous use of low-dose anti-cancer drugs, resulting in histological changes similar to those seen after NAC.},
}

Aged
Antirheumatic Agents/*therapeutic use
Arthritis, Rheumatoid/complications/*drug therapy
Breast/*pathology
Breast Neoplasms/complications/*pathology/*therapy
Carcinoma, Intraductal, Noninfiltrating/complications/*pathology/*therapy
*Chemotherapy, Adjuvant
Female
Humans
Lymph Nodes/pathology
Mastectomy
Methotrexate/*therapeutic use
Middle Aged
*Neoadjuvant Therapy

@article {pmid28693516,
year = {2017},
author = {Sun, X and Zuo, K and Huang, D and Yu, B and Cheng, Y and Yang, W},
title = {Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.},
journal = {Diagnostic pathology},
volume = {12},
number = {1},
pages = {52},
pmid = {28693516},
issn = {1746-1596},
mesh = {Biomarkers, Tumor/metabolism ; Breast/pathology ; Breast Neoplasms/diagnosis/*pathology ; Carcinoma, Ductal, Breast/diagnosis/*pathology ; Carcinoma, Lobular/*secondary ; Female ; Humans ; Immunohistochemistry/methods ; Middle Aged ; Pancreatic Neoplasms/*secondary ; Receptors, Progesterone ; },
abstract = {BACKGROUND: Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare.

CASE PRESENTATION: We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast.

CONCLUSIONS: To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.},
}

Biomarkers, Tumor/metabolism
Breast/pathology
Breast Neoplasms/diagnosis/*pathology
Carcinoma, Ductal, Breast/diagnosis/*pathology
Carcinoma, Lobular/*secondary
Female
Humans
Immunohistochemistry/methods
Middle Aged
Pancreatic Neoplasms/*secondary
Receptors, Progesterone

@article {pmid28700421,
year = {2018},
author = {Xing, D and Jenson, EG and Zwick, CA and Rodriguez, FJ and Kurman, RJ},
title = {Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {37},
number = {1},
pages = {52-56},
doi = {10.1097/PGP.0000000000000389},
pmid = {28700421},
issn = {1538-7151},
mesh = {Biomarkers, Tumor/metabolism ; Biopsy ; Brain/pathology ; Brain Neoplasms/diagnostic imaging/pathology/*secondary ; Breast Neoplasms/*pathology/surgery ; Cell Proliferation ; Cystadenocarcinoma, Serous/diagnostic imaging/pathology/*secondary/surgery ; Cystadenofibroma/diagnostic imaging/*pathology/surgery ; Diagnosis, Differential ; Encephalomalacia/diagnostic imaging/pathology/surgery ; Epithelial Cells/pathology ; Fallopian Tubes/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Ovarian Neoplasms/*pathology/surgery ; Salpingo-oophorectomy ; },
abstract = {A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefore, interpreted as a small area of encephalomalacia related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for ovarian tumors that were diagnosed as bilateral serous cystadenofibromas. A partial omentectomy showed no evidence of implants. In June 2016, the brain lesion was completely excised and diagnosed as an atypical proliferative (borderline) serous tumor. Immunohistochemical staining demonstrated that the tumor cells were immunoreactive for Pax8, WT-1, ER, and CK-7 and negative for Gata-3, PR, TTF-1, CDX-2, Napsin A, and CK-20, which was consistent with that diagnosis. We present a brief review of possible mechanisms to account for this unusual presentation and speculate that the most likely one is exfoliation of fallopian tube epithelial cells into the peritoneal cavity, which then gain access to lymphatics resulting in cells implanting in the brain and subsequently progressing to an atypical proliferative (borderline) serous tumor.},
}

Biomarkers, Tumor/metabolism
Biopsy
Brain/pathology
Brain Neoplasms/diagnostic imaging/pathology/*secondary
Breast Neoplasms/*pathology/surgery
Cell Proliferation
Cystadenocarcinoma, Serous/diagnostic imaging/pathology/*secondary/surgery
Cystadenofibroma/diagnostic imaging/*pathology/surgery
Diagnosis, Differential
Encephalomalacia/diagnostic imaging/pathology/surgery
Epithelial Cells/pathology
Fallopian Tubes/pathology
Female
Humans
Immunohistochemistry
Lymphatic Metastasis
Middle Aged
Ovarian Neoplasms/*pathology/surgery
Salpingo-oophorectomy

@article {pmid28702871,
year = {2018},
author = {Hirayama, K and Kono, H and Nakata, Y and Akazawa, Y and Wakana, H and Fukushima, H and Fujii, H},
title = {Expression of podoplanin in stromal fibroblasts plays a pivotal role in the prognosis of patients with pancreatic cancer.},
journal = {Surgery today},
volume = {48},
number = {1},
pages = {110-118},
pmid = {28702871},
issn = {1436-2813},
mesh = {Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/*genetics/mortality/*pathology ; Disease-Free Survival ; Female ; Fibroblasts/*metabolism/*pathology ; *Gene Expression ; Humans ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/*genetics/*metabolism ; Middle Aged ; Pancreatic Neoplasms/*genetics/mortality/*pathology ; Prognosis ; Proportional Hazards Models ; Risk Factors ; Podoplanin ; },
abstract = {PURPOSE: To investigate the role of podoplanin (PDPN) expression in invasive ductal carcinoma of the pancreas (IDCP) in humans.

METHODS: Tumor samples were obtained from 95 patients with IDCP. Immunohistochemical staining was done to evaluate the expression of PDPN in cancer tissues.

RESULTS: PDPN was detected predominantly in stromal fibroblasts, stained with α-smooth muscle actin. The cutoff value of PDPN-positive areas was calculated according to a histogram. There was no significant difference in clinicopathologic factors between patients with high vs. those with low PDPN expression. The high PDPN group showed significantly poorer disease-free and disease-specific survival rates than the low PDPN group. Among patients from the high PDPN group, those with lymph node metastases and those with a tumor larger than 20 cm in diameter had significantly poorer prognoses than similar patients from the low PDPN group. Multivariate Cox proportional hazards analysis indicated that a high expression of PDPN was an independent risk factor for disease-specific survival.

CONCLUSIONS: PDPN expression in cancer-related fibrotic tissues is associated with a poor prognosis, especially in patients with large tumors or lymph node metastases.},
}

Aged
Aged, 80 and over
Carcinoma, Pancreatic Ductal/*genetics/mortality/*pathology
Disease-Free Survival
Female
Fibroblasts/*metabolism/*pathology
*Gene Expression
Humans
Lymphatic Metastasis
Male
Membrane Glycoproteins/*genetics/*metabolism
Middle Aged
Pancreatic Neoplasms/*genetics/mortality/*pathology
Prognosis
Proportional Hazards Models
Risk Factors
Podoplanin

@article {pmid28709865,
year = {2017},
author = {Wan, G and Tian, L and Yu, Y and Li, F and Wang, X and Li, C and Deng, S and Yu, X and Cai, X and Zuo, Z and Cao, F},
title = {Overexpression of Pofut1 and activated Notch1 may be associated with poor prognosis in breast cancer.},
journal = {Biochemical and biophysical research communications},
volume = {491},
number = {1},
pages = {104-111},
doi = {10.1016/j.bbrc.2017.07.053},
pmid = {28709865},
issn = {1090-2104},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/*metabolism/*mortality/pathology ; China/epidemiology ; Female ; Fucosyltransferases/*metabolism ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Prevalence ; Prognosis ; Receptor, Notch1/*metabolism ; Reproducibility of Results ; Risk Factors ; Sensitivity and Specificity ; Survival Rate ; Up-Regulation ; },
abstract = {PURPOSE: The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer.

MATERIAL AND METHODS: Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter.

RESULTS: Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome.

CONCLUSION: Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.},
}

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor/*metabolism
Breast Neoplasms/*metabolism/*mortality/pathology
China/epidemiology
Female
Fucosyltransferases/*metabolism
Humans
Middle Aged
Neoplasm Invasiveness
Prevalence
Prognosis
Receptor, Notch1/*metabolism
Reproducibility of Results
Risk Factors
Sensitivity and Specificity
Survival Rate
Up-Regulation

@article {pmid28710742,
year = {2018},
author = {Avnon, A and Orkaby, N and Hadas, A and Berger, U and Brunstein Klomek, A and Fennig, S},
title = {Inpatient weight curve trajectory as a prognostic factor among adolescents with anorexia nervosa: a preliminary report.},
journal = {Eating and weight disorders : EWD},
volume = {23},
number = {5},
pages = {645-651},
pmid = {28710742},
issn = {1590-1262},
mesh = {Adolescent ; Anorexia Nervosa/physiopathology/*therapy ; Body Mass Index ; Body Weight/*physiology ; Child ; Female ; Humans ; *Inpatients ; Male ; Patient Discharge ; Prognosis ; Recurrence ; Risk Factors ; Treatment Outcome ; Weight Gain/*physiology ; },
abstract = {OBJECTIVE: To investigate the predictive value of weight restoration trajectories for relapse within the first year after discharge from inpatient treatment among adolescents with AN.

METHODS: Forty four inpatient adolescents (5 boys, 39 girls) aged 11-18 (M 14.85, SD 1.87) diagnosed with anorexia were assessed at admission and discharge from a general hospital inpatient ward. Re-hospitalizations within 1 year of discharge were recorded. Factors assessed included 1/BMI at admission, 2/BMI at discharge, 3/percent from target weight (PFTW) at discharge, 4/length of hospitalization, and 5/a weight restoration trajectory measuring weight drops during inpatient weight restoration (rates of negative cubic variation in body weight (NCV).

RESULTS: Logistic regression indicated that negative cubic variation rates (NCV) predicted re-hospitalization. PFTW was found only marginally significant.

CONCLUSION: Variations in weight restoration during inpatient treatment may be used to identify patients at risk for relapse. NCV can alert clinicians to initiate early relapse prevention interventions before discharge. Level of Evidence Level III, cohort study.},
}

Adolescent
Anorexia Nervosa/physiopathology/*therapy
Body Mass Index
Body Weight/*physiology
Child
Female
Humans
*Inpatients
Male
Patient Discharge
Prognosis
Recurrence
Risk Factors
Treatment Outcome
Weight Gain/*physiology

@article {pmid28717182,
year = {2017},
author = {Bjørklund, SS and Panda, A and Kumar, S and Seiler, M and Robinson, D and Gheeya, J and Yao, M and Alnæs, GIG and Toppmeyer, D and Riis, M and Naume, B and Børresen-Dale, AL and Kristensen, VN and Ganesan, S and Bhanot, G},
title = {Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma.},
journal = {Scientific reports},
volume = {7},
number = {1},
pages = {5568},
pmid = {28717182},
issn = {2045-2322},
mesh = {*Alternative Splicing ; Breast Neoplasms/*genetics/metabolism ; Carcinoma, Ductal, Breast/*genetics/metabolism ; Cohort Studies ; Databases, Genetic ; Exons ; Female ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Sequence Analysis, RNA/methods ; },
abstract = {Cancer cells can have different patterns of exon usage of individual genes when compared to normal tissue, suggesting that alternative splicing may play a role in shaping the tumor phenotype. The discovery and identification of gene variants has increased dramatically with the introduction of RNA-sequencing technology, which enables whole transcriptome analysis of known, as well as novel isoforms. Here we report alternative splicing and transcriptional events among subtypes of invasive ductal carcinoma in The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) cohort. Alternative exon usage was widespread, and although common events were shared among three subtypes, ER+ HER2-, ER- HER2-, and HER2+, many events on the exon level were subtype specific. Additional RNA-seq analysis was carried out in an independent cohort of 43 ER+ HER2- and ER- HER2- primary breast tumors, confirming many of the exon events identified in the TCGA cohort. Alternative splicing and transcriptional events detected in five genes, MYO6, EPB41L1, TPD52, IQCG, and ACOX2 were validated by qRT-PCR in a third cohort of 40 ER+ HER2- and ER- HER2- patients, showing that these events were truly subtype specific.},
}

*Alternative Splicing
Breast Neoplasms/*genetics/metabolism
Carcinoma, Ductal, Breast/*genetics/metabolism
Cohort Studies
Databases, Genetic
Exons
Female
Gene Expression Profiling/*methods
Gene Expression Regulation, Neoplastic
Humans
Erb-b2 Receptor Tyrosine Kinases/metabolism
Receptors, Estrogen/metabolism
Sequence Analysis, RNA/methods

@article {pmid28719381,
year = {2018},
author = {Oliveira, RV and Souza, VB and Souza, PC and Soares, FA and Vassallo, J and Rocha, RM and Schenka, AA},
title = {Detection of Putative Stem-cell Markers in Invasive Ductal Carcinoma of the Breast by Immunohistochemistry: Does It Improve Prognostic/Predictive Assessments?.},
journal = {Applied immunohistochemistry & molecular morphology : AIMM},
volume = {26},
number = {10},
pages = {760-768},
pmid = {28719381},
issn = {1533-4058},
mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*metabolism ; Brazil ; Breast Neoplasms/metabolism/mortality/pathology ; *Carcinoma, Ductal, Breast/metabolism/mortality/pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Proteins/*metabolism ; Risk Factors ; Survival Rate ; },
abstract = {INTRODUCTION: Experimental evidences from the last 2 decades supports the existence of a special type of neoplastic cell with stem-like features [cancer stem cell (CSC)] and their role in the pathophysiology and therapeutic resistance of breast cancer. However, their clinical value in human breast cancer has not been fully determined.

MATERIALS AND METHODS: An immunohistochemistry panel of 10 putative CSC markers (CD34, C-KIT, CD10, SOX-2, OCT 3/4, p63, CD24, CD44, CD133, and ESA/EPCAM) was applied to 74 cases of breast cancer, followed in a Regional Cancer Center of Minas Gerais State, Brazil, from 2004 to 2006. Possible associations between CSC markers and classic variables of clinicopathologic relevance were investigated.

RESULTS: The most frequently positive CSC markers were CD44, CD24, CD133, and ESA (the others were present in <15% of the cases). Two CSC profiles were defined: CD24/CD44 (CSC-1) and CD133/ESA (CSC-2). CSC-1 was significantly associated to patients older than 40 years, tumors of <2.0 cm in diameter, early clinical stages (P<0.05), and increased death risk of 4 times (P=0.03; 95% confidence interval, 1.09-14.41). CSC-2 was related to increased relapse risk of 3.75 times (P=0.04; 95% confidence interval, 1.02-13.69).

CONCLUSION: The detection of the most frequently positive CSC markers by immunohistochemistry is of clinicopathologic and prognostic relevance.},
}

Adult
Age Factors
Aged
Aged, 80 and over
Biomarkers, Tumor/*metabolism
Brazil
Breast Neoplasms/metabolism/mortality/pathology
*Carcinoma, Ductal, Breast/metabolism/mortality/pathology
Disease-Free Survival
Female
Humans
Immunohistochemistry
Middle Aged
Neoplasm Invasiveness
Neoplasm Proteins/*metabolism
Risk Factors
Survival Rate

@article {pmid28726282,
year = {2017},
author = {Horikawa, H and Umegaki-Arao, N and Funakoshi, T and Amagai, M and Tanaka, M},
title = {Dermoscopy of pigmented invasive ductal carcinoma mimicking basal cell carcinoma.},
journal = {The Australasian journal of dermatology},
volume = {58},
number = {4},
pages = {326-327},
doi = {10.1111/ajd.12671},
pmid = {28726282},
issn = {1440-0960},
mesh = {Breast Neoplasms/*pathology ; Basal Cell Carcinoma/*diagnostic imaging ; Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary ; *Dermoscopy ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Nipples ; Skin Neoplasms/*diagnostic imaging/pathology/secondary ; Skin Pigmentation ; },
}

Breast Neoplasms/*pathology
Basal Cell Carcinoma/*diagnostic imaging
Carcinoma, Ductal, Breast/*diagnostic imaging/pathology/secondary
*Dermoscopy
Diagnosis, Differential
Female
Humans
Middle Aged
Nipples
Skin Neoplasms/*diagnostic imaging/pathology/secondary
Skin Pigmentation

@article {pmid28730339,
year = {2017},
author = {Santiago, L and Adrada, BE and Huang, ML and Wei, W and Candelaria, RP},
title = {Breast cancer neoplastic seeding in the setting of image-guided needle biopsies of the breast.},
journal = {Breast cancer research and treatment},
volume = {166},
number = {1},
pages = {29-39},
doi = {10.1007/s10549-017-4401-7},
pmid = {28730339},
issn = {1573-7217},
mesh = {Biomarkers, Tumor/metabolism ; Breast Neoplasms/*diagnostic imaging/metabolism/mortality/*pathology ; Female ; Humans ; Image-Guided Biopsy ; Mammography ; Neoplasm Grading ; Neoplasm Seeding ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Time Factors ; Triple Negative Breast Neoplasms/diagnostic imaging/metabolism/mortality/pathology ; },
abstract = {PURPOSE: To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy.

METHODS: We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS.

RESULTS: Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8 days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal.

CONCLUSION: High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.},
}

Biomarkers, Tumor/metabolism
Breast Neoplasms/*diagnostic imaging/metabolism/mortality/*pathology
Female
Humans
Image-Guided Biopsy
Mammography
Neoplasm Grading
Neoplasm Seeding
Neoplasm Staging
Prognosis
Retrospective Studies
Risk Factors
Time Factors
Triple Negative Breast Neoplasms/diagnostic imaging/metabolism/mortality/pathology

@article {pmid28732472,
year = {2017},
author = {Kulkarni, S and Jadhav, S and Khopkar, P and Sane, S and Londhe, R and Chimanpure, V and Dhilpe, V and Ghate, M and Yelagate, R and Panchal, N and Rahane, G and Kadam, D and Gaikwad, N and Rewari, B and Gangakhedkar, R},
title = {GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.},
journal = {BMC infectious diseases},
volume = {17},
number = {1},
pages = {506},
pmid = {28732472},
issn = {1471-2334},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Antiretroviral Therapy, Highly Active ; Case-Control Studies ; HIV Infections/*drug therapy/*virology ; *HIV-1/genetics/pathogenicity ; Humans ; India ; Point-of-Care Systems ; Real-Time Polymerase Chain Reaction/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Viral Load/*methods ; },
abstract = {BACKGROUND: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings.

METHODS: A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure.

RESULTS: The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p < 0.01), the linear regression showed a moderate fit (R[2] = 0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p = 0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R[2] = 0.896 to 0.982).

CONCLUSION: The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1 m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.},
}

Antiretroviral Therapy, Highly Active
Case-Control Studies
HIV Infections/*drug therapy/*virology
*HIV-1/genetics/pathogenicity
Humans
India
Point-of-Care Systems
Real-Time Polymerase Chain Reaction/methods
Reproducibility of Results
Sensitivity and Specificity
Viral Load/*methods

@article {pmid28755148,
year = {2017},
author = {Meng, F and Liu, B and Xie, G and Song, Y and Zheng, X and Qian, X and Li, S and Jia, H and Zhang, X and Zhang, L and Yang, YL and Fu, L},
title = {Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.},
journal = {Breast cancer research and treatment},
volume = {166},
number = {2},
pages = {383-392},
doi = {10.1007/s10549-017-4407-1},
pmid = {28755148},
issn = {1573-7217},
mesh = {Adult ; Aged ; Antigens, Neoplasm/*genetics/*metabolism ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics/*metabolism ; Carcinoma, Papillary/genetics/*metabolism ; Cell Adhesion Molecules/metabolism ; Chromosomes, Human, Pair 8/genetics ; Female ; GPI-Linked Proteins/genetics/metabolism ; *Gene Amplification ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Neoplasm Proteins/*genetics/*metabolism ; Prognosis ; Survival Analysis ; *Up-Regulation ; },
abstract = {PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied.

METHODS: Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis.

RESULTS: PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant rate of the immunohistochemistry and FISH data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs = 0.687, P < 0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P = 0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P = 0.022).

CONCLUSIONS: Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.},
}

Adult
Aged
Antigens, Neoplasm/*genetics/*metabolism
Biomarkers, Tumor/genetics
Breast Neoplasms/genetics/*metabolism
Carcinoma, Papillary/genetics/*metabolism
Cell Adhesion Molecules/metabolism
Chromosomes, Human, Pair 8/genetics
Female
GPI-Linked Proteins/genetics/metabolism
*Gene Amplification
Gene Expression Regulation, Neoplastic
Humans
In Situ Hybridization, Fluorescence
Middle Aged
Neoplasm Proteins/*genetics/*metabolism
Prognosis
Survival Analysis
*Up-Regulation

@article {pmid28765906,
year = {2017},
author = {Wang, J and Song, L and Yang, S and Zhang, W and Lu, P and Li, S and Li, H and Wang, L},
title = {HPK1 positive expression associated with longer overall survival in patients with estrogen receptor-positive invasive ductal carcinoma‑not otherwise specified.},
journal = {Molecular medicine reports},
volume = {16},
number = {4},
pages = {4634-4642},
pmid = {28765906},
issn = {1791-3004},
mesh = {Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms/*genetics/*mortality/pathology ; Carcinoma, Ductal, Breast/*genetics/*mortality/pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Protein Serine-Threonine Kinases/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Receptors, Progesterone/metabolism ; Survival Analysis ; },
abstract = {Hematopoietic progenitor kinase 1 (HPK1) belongs to the mitogen activated protein kinase kinase kinase kinase (MAP4K) family of serine/threonine kinases, which have been associated with the incidence and progression of a variety of gastrointestinal malignant tumors in humans. However, the potential association between HPK1 expression and breast cancer, particularly invasive ductal carcinoma‑not otherwise specified (IDC‑NOS) development, has not yet been examined. To address this gap, the present study aimed to evaluate HPK1 expression in IDC‑NOS samples and to determine a relationship with clinical prognostic indicators, such as the expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as overall survival of the patients with IDC‑NOS. HPK1 mRNA and protein expression in samples from 148 patients with IDC‑NOS were detected using immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. A total of 54 out of 148 (36.5%) samples were HPK1‑positive, and 100 out of 148 (67.6%) were ER‑positive. Of the latter, 28% (28/100) were HPK1‑positive, and a significant negative association of HPK1 expression with ER positivity was observed (P=0.002; r=‑0.254). In addition, 43.2% (64/148) and 32.4% (48/100) of IDC‑NOS tissues were PR‑ or HER2‑positive, respectively; however, neither indicator correlated with HPK1 (P=0.109 and P=0.558, respectively). HPK1 expression, axillary lymph node metastasis and tumor‑node‑metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER‑positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048). HPK1 mRNA levels did not differ between IDC‑NOS and normal adjacent breast tissues, whereas HPK1 protein levels were lower in IDC‑NOS (P<0.05). These results suggested that HPK1 protein may be a potentially effective IDC-NOS therapeutic target.},
}

Adult
Aged
Biomarkers, Tumor
Breast Neoplasms/*genetics/*mortality/pathology
Carcinoma, Ductal, Breast/*genetics/*mortality/pathology
Female
Gene Expression
Humans
Immunohistochemistry
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Protein Serine-Threonine Kinases/*genetics/metabolism
RNA, Messenger/genetics/metabolism
Erb-b2 Receptor Tyrosine Kinases/metabolism
Receptors, Estrogen/*genetics/metabolism
Receptors, Progesterone/metabolism
Survival Analysis

@article {pmid28801774,
year = {2017},
author = {Escórcio-Dourado, CS and Martins, LM and Simplício-Revoredo, CM and Sampaio, FA and Tavares, CB and da Silva-Sampaio, JP and Borges, US and Alves-Ribeiro, FA and Lopes-Costa, PV and Lima-Dourado, JC and da Silva, BB},
title = {Bcl-2 antigen expression in luminal A and triple-negative breast cancer.},
journal = {Medical oncology (Northwood, London, England)},
volume = {34},
number = {9},
pages = {161},
pmid = {28801774},
issn = {1559-131X},
mesh = {Adult ; Antigens/metabolism ; Biomarkers, Tumor/immunology/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*immunology/metabolism ; Triple Negative Breast Neoplasms/*immunology/*pathology ; },
abstract = {Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher's exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.},
}

Adult
Antigens/metabolism
Biomarkers, Tumor/immunology/metabolism
Female
Humans
Immunohistochemistry
Middle Aged
Proto-Oncogene Proteins c-bcl-2/*immunology/metabolism
Triple Negative Breast Neoplasms/*immunology/*pathology

@article {pmid28826004,
year = {2017},
author = {Zemva, J and Fink, CA and Fleming, TH and Schmidt, L and Loft, A and Herzig, S and Knieß, RA and Mayer, M and Bukau, B and Nawroth, PP and Tyedmers, J},
title = {Hormesis enables cells to handle accumulating toxic metabolites during increased energy flux.},
journal = {Redox biology},
volume = {13},
number = {},
pages = {674-686},
pmid = {28826004},
issn = {2213-2317},
mesh = {Amino Acid Transport Systems/metabolism ; *Energy Metabolism ; Glucose/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; *Hormesis ; Pyruvaldehyde/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Vesicular Transport Proteins ; Heat-Shock Proteins, Small ; },
abstract = {Energy production is inevitably linked to the generation of toxic metabolites, such as reactive oxygen and carbonyl species, known as major contributors to ageing and degenerative diseases. It remains unclear how cells can adapt to elevated energy flux accompanied by accumulating harmful by-products without taking any damage. Therefore, effects of a sudden rise in glucose concentrations were studied in yeast cells. This revealed a feedback mechanism initiated by the reactive dicarbonyl methylglyoxal, which is formed non-enzymatically during glycolysis. Low levels of methylglyoxal activate a multi-layered defence response against toxic metabolites composed of prevention, detoxification and damage remission. The latter is mediated by the protein quality control system and requires inducible Hsp70 and Btn2, the aggregase that sequesters misfolded proteins. This glycohormetic mechanism enables cells to pre-adapt to rising energy flux and directly links metabolic to proteotoxic stress. Further data suggest the existence of a similar response in endothelial cells.},
}

Amino Acid Transport Systems/metabolism
*Energy Metabolism
Glucose/metabolism
HSP70 Heat-Shock Proteins/metabolism
*Hormesis
Pyruvaldehyde/*metabolism
Saccharomyces cerevisiae/genetics/metabolism
Saccharomyces cerevisiae Proteins/metabolism
Vesicular Transport Proteins
Heat-Shock Proteins, Small

@article {pmid28830512,
year = {2017},
author = {Gupta, AP and Zhu, L and Tripathi, J and Kucharski, M and Patra, A and Bozdech, Z},
title = {Histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in Plasmodium falciparum.},
journal = {Epigenetics & chromatin},
volume = {10},
number = {1},
pages = {40},
pmid = {28830512},
issn = {1756-8935},
mesh = {Acetylation ; *Cell Proliferation ; Chromatin/metabolism ; Erythrocytes/parasitology ; Histones/*metabolism ; *Host-Parasite Interactions ; Humans ; Open Reading Frames ; Plasmodium falciparum/*genetics/pathogenicity ; Promoter Regions, Genetic ; *Protein Processing, Post-Translational ; Protozoan Proteins/*metabolism ; },
abstract = {BACKGROUND: The dynamics of histone modifications in Plasmodium falciparum indicates the existence of unique mechanisms that link epigenetic factors with transcription. Here, we studied the impact of acetylated histone code on transcriptional regulation during the intraerythrocytic developmental cycle (IDC) of P. falciparum.

RESULTS: Using a dominant-negative transgenic approach, we showed that acetylations of histone H4 play a direct role in transcription. Specifically, these histone modifications mediate an inverse transcriptional relationship between the factors of cell proliferation and host-parasite interaction. Out of the four H4 acetylations, H4K8ac is likely the rate-limiting, regulatory step, which modulates the overall dynamics of H4 posttranslational modifications. H4K8ac exhibits maximum responsiveness to HDAC inhibitors and has a highly dynamic distribution pattern along the genome of P. falciparum during the IDC. Moreover, H4K8ac functions mainly in the euchromatin where its occupancy shifts from intergenic regions located upstream of 5' end of open reading frame into the protein coding regions. This shift is directly or indirectly associated with transcriptional activities at the corresponding genes. H4K8ac is also active in the heterochromatin where it stimulates expression of the main antigenic gene family (var) by its presence in the promoter region.

CONCLUSIONS: Overall, we demonstrate that H4K8ac is a potential major regulator of chromatin-linked transcriptional changes during P. falciparum life cycle which is associated not only with euchromatin but also with heterochromatin environment. This is potentially a highly significant finding that suggests a regulatory connection between growth and parasite-host interaction both of which play a major role in malaria parasite virulence.},
}

Acetylation
*Cell Proliferation
Chromatin/metabolism
Erythrocytes/parasitology
Histones/*metabolism
*Host-Parasite Interactions
Humans
Open Reading Frames
Plasmodium falciparum/*genetics/pathogenicity
Promoter Regions, Genetic
*Protein Processing, Post-Translational
Protozoan Proteins/*metabolism

@article {pmid28843709,
year = {2018},
author = {Karnik, T and Kimler, BF and Fan, F and Tawfik, O},
title = {PD-L1 in breast cancer: comparative analysis of 3 different antibodies.},
journal = {Human pathology},
volume = {72},
number = {},
pages = {28-34},
doi = {10.1016/j.humpath.2017.08.010},
pmid = {28843709},
issn = {1532-8392},
mesh = {Antibodies, Monoclonal/immunology/*therapeutic use ; B7-H1 Antigen/*immunology ; Biomarkers, Tumor/analysis ; Breast Neoplasms/*drug therapy/immunology ; Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology ; Immunohistochemistry/methods ; Lung Neoplasms/*drug therapy/immunology/pathology ; Treatment Outcome ; },
abstract = {The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.},
}

Antibodies, Monoclonal/immunology/*therapeutic use
B7-H1 Antigen/*immunology
Biomarkers, Tumor/analysis
Breast Neoplasms/*drug therapy/immunology
Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
Immunohistochemistry/methods
Lung Neoplasms/*drug therapy/immunology/pathology
Treatment Outcome

@article {pmid28860708,
year = {2017},
author = {Li, A and Li, Y and Ge, L and Li, P and Li, W},
title = {Onychomadesis associated with chemotherapy: case report and mini literature review.},
journal = {Drug design, development and therapy},
volume = {11},
number = {},
pages = {2373-2376},
pmid = {28860708},
issn = {1177-8881},
mesh = {Aged ; Albumins/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects ; Breast Neoplasms/therapy ; Capecitabine/administration & dosage ; Carcinoma, Ductal, Breast/therapy ; Female ; Follow-Up Studies ; Humans ; Nail Diseases/*chemically induced/pathology/therapy ; Paclitaxel/administration & dosage ; },
abstract = {The side effects of chemotherapy drugs have increased in recent years, and some side effects can lead to onychomadesis. A 72-year-old woman who was diagnosed with an invasive ductal carcinoma of the right breast underwent a modified radical mastectomy in April 2015, followed by chemotherapy with capecitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Subsequently, the patient experienced palmoplantar redness, pain, onycholysis, a transparent serous exudate, and onychomadesis. The chemotherapy was discontinued, and the patient was treated with oral vitamin B6, a polymyxin ointment, and a high-energy red light. The palmoplantar redness and pain were alleviated after 1 month. However, although her fingernails improved, dysesthesia symptoms remained, and all her toenails exhibited defects or deformities at a 24-month follow-up. The symptoms of this disorder should be recognized by dermatologists.},
}

Aged
Albumins/administration & dosage
Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects
Breast Neoplasms/therapy
Capecitabine/administration & dosage
Carcinoma, Ductal, Breast/therapy
Female
Follow-Up Studies
Humans
Nail Diseases/*chemically induced/pathology/therapy
Paclitaxel/administration & dosage

@article {pmid28862125,
year = {2017},
author = {Stroescu, C and Gilca, I and Chirita, D and Poenaru, R and Puşcaşu, A and Pescaru, D and Birceanu, A and Niţipir, C and Copcă, N},
title = {Solitary Adrenal Metastases from Breast Invasive Ductal Carcinoma.},
journal = {Chirurgia (Bucharest, Romania : 1990)},
volume = {112},
number = {4},
pages = {473-476},
doi = {10.21614/chirurgia.112.4.473},
pmid = {28862125},
issn = {1221-9118},
mesh = {Adrenal Gland Neoplasms/*secondary/surgery ; *Adrenalectomy ; Aged ; Breast Neoplasms/*pathology/surgery ; Carcinoma, Ductal, Breast/*secondary/surgery ; Female ; Humans ; Neoplasm Invasiveness ; Treatment Outcome ; },
abstract = {The usual neoplastic dissease involving suprarenal glands are adrenal metastaes. The majority of suprarenal metastatic disease arise from lung cancer, followed by the stomach and colon cancer, oesophagus, the liver/bile ducts cancer and renal cell carcinoma. Invasive mammary carcinoma usually spreads to the bones, lungs, lymph nodes, liver and the brain. Adrenal gland metastases from invasive no special type carcinoma represents an extremly low rate number of cases. We discuss about a 66 year old patient who presented with a solitary adrenal metastases from triple negative breast invasive carcinoma. The patient underwent total left adrenalectomy in June 2016. No further adjuvants therapies were performed. At the time of writing the patient is in good condition, without any evidence of recurrence. The role of surgical and adjuvant therapy in treating adrenal metastases after breast cancer in survival rate will be determined in future studies.},
}

Adrenal Gland Neoplasms/*secondary/surgery
*Adrenalectomy
Aged
Breast Neoplasms/*pathology/surgery
Carcinoma, Ductal, Breast/*secondary/surgery
Female
Humans
Neoplasm Invasiveness
Treatment Outcome

@article {pmid28869838,
year = {2017},
author = {Turczyk, L and Kitowska, K and Mieszkowska, M and Mieczkowski, K and Czaplinska, D and Piasecka, D and Kordek, R and Skladanowski, AC and Potemski, P and Romanska, HM and Sadej, R},
title = {FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells.},
journal = {Neoplasia (New York, N.Y.)},
volume = {19},
number = {10},
pages = {791-804},
pmid = {28869838},
issn = {1476-5586},
mesh = {Biomarkers, Tumor ; Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Estrogen Receptor alpha/*metabolism ; Female ; Fibroblast Growth Factors/metabolism ; Fibroblasts/drug effects ; Gene Expression ; Gene Knockout Techniques ; Humans ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Proteolysis ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/genetics/*metabolism ; Selective Estrogen Receptor Modulators/*pharmacology ; Signal Transduction/*drug effects ; Tamoxifen/*pharmacology ; },
abstract = {Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.},
}

Biomarkers, Tumor
Breast Neoplasms/genetics/metabolism/pathology
Cell Line, Tumor
Estrogen Receptor alpha/*metabolism
Female
Fibroblast Growth Factors/metabolism
Fibroblasts/drug effects
Gene Expression
Gene Knockout Techniques
Humans
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Proteolysis
Erb-b2 Receptor Tyrosine Kinases/metabolism
Receptor, Fibroblast Growth Factor, Type 2/genetics/*metabolism
Selective Estrogen Receptor Modulators/*pharmacology
Signal Transduction/*drug effects
Tamoxifen/*pharmacology

@article {pmid28899737,
year = {2017},
author = {Cao, L and Sun, PL and Yao, M and Jia, M and Gao, H},
title = {Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues.},
journal = {Human pathology},
volume = {68},
number = {},
pages = {166-174},
doi = {10.1016/j.humpath.2017.08.032},
pmid = {28899737},
issn = {1532-8392},
mesh = {Adaptor Proteins, Signal Transducing/*analysis ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*analysis ; Biopsy ; Breast Neoplasms/*chemistry/mortality/pathology/therapy ; Carcinoma/*chemistry/mortality/secondary/therapy ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Phosphoproteins/*analysis ; Proportional Hazards Models ; Erb-b2 Receptor Tyrosine Kinases/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Transcription Factors ; YAP-Signaling Proteins ; },
abstract = {The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor, progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan-Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival in patients with luminal A breast cancer and with favorable DFS association among patients with invasive ductal carcinoma, luminal B (HER2-), and luminal B (HER2+) breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and overall survival, respectively, among patients with breast cancer, whereas tumor-node-metastasis stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.},
}

Adaptor Proteins, Signal Transducing/*analysis
Adult
Age Factors
Aged
Aged, 80 and over
Biomarkers, Tumor/*analysis
Biopsy
Breast Neoplasms/*chemistry/mortality/pathology/therapy
Carcinoma/*chemistry/mortality/secondary/therapy
Disease-Free Survival
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Ki-67 Antigen/analysis
Lymphatic Metastasis
Middle Aged
Multivariate Analysis
Neoplasm Staging
Phosphoproteins/*analysis
Proportional Hazards Models
Erb-b2 Receptor Tyrosine Kinases/analysis
Receptors, Progesterone/analysis
Retrospective Studies
Risk Factors
Time Factors
Transcription Factors
YAP-Signaling Proteins

@article {pmid28902360,
year = {2017},
author = {Ratajczak-Wielgomas, K and Grzegrzolka, J and Piotrowska, A and Matkowski, R and Wojnar, A and Rys, J and Ugorski, M and Dziegiel, P},
title = {Expression of periostin in breast cancer cells.},
journal = {International journal of oncology},
volume = {51},
number = {4},
pages = {1300-1310},
doi = {10.3892/ijo.2017.4109},
pmid = {28902360},
issn = {1791-2423},
mesh = {Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Ductal, Breast/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Cell Adhesion Molecules/*genetics/*metabolism ; Cell Line, Tumor ; Cytoplasm/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Middle Aged ; Tumor Burden ; Up-Regulation ; },
abstract = {Periostin (POSTN) is a protein involved in multiple processes important for cancer development, both at the stage of cancer initiation and progression, as well as metastasis. The aim of this study was to determine the expression of POSTN in the cells of non-invasive ductal breast carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to correlate it with clinicopathological data. Immunohistochemical studies (IHC) were conducted on 21 cases of fibrocystic breast change (FC), 44 cases of DCIS and 92 cases of IDC. POSTN expression at mRNA (real-time PCR) and protein level (western blot analysis) was also confirmed in selected breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2). Statistically significant higher level of POSTN expression in IDC and DCIS cancer cells compared to FC was noted. Also, the level of POSTN expression in the cytoplasm of IDC cells was shown to increase with the increasing degree of tumour malignancy (G) and significantly higher expression of POSTN was observed in each degree of tumour malignancy (G) relative to FC. Statistically significant higher POSTN expression was observed in tumours with estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) phenotypes in comparison to estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cases, as well as significant negative correlation between POSTN expression in cancer cells and expression of ER and PR (p<0.05). Additionally, statistically significant differences in POSTN expression were shown between particular breast cancer cell lines, both at mRNA and protein level. Observed POSTN expression was the lowest in the case of MCF-7, and the highest in MDA-MB-231 and BO2 of the most aggressive potential clinically corresponding to G3 tumours. POSTN expression in the cytoplasm of IDC cancer cells may play an important role in cancer transformation mechanism.},
}

Breast Neoplasms/genetics/metabolism/*pathology
Carcinoma, Ductal, Breast/genetics/metabolism/*pathology
Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology
Cell Adhesion Molecules/*genetics/*metabolism
Cell Line, Tumor
Cytoplasm/metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
MCF-7 Cells
Middle Aged
Tumor Burden
Up-Regulation

@article {pmid28906374,
year = {2017},
author = {Golmohammadi, R and Namazi, MJ and Going, JJ and Derakhshan, MH},
title = {A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.},
journal = {Medicine},
volume = {96},
number = {37},
pages = {e7933},
pmid = {28906374},
issn = {1536-5964},
mesh = {Adult ; Aged ; Aged, 80 and over ; Aurora Kinase A/*genetics ; Breast Neoplasms/*genetics/mortality/*pathology ; Carcinoma, Ductal, Breast/*genetics/mortality/*pathology ; Case-Control Studies ; Codon ; Female ; Humans ; Iran ; Middle Aged ; Neoplasm Invasiveness ; *Polymorphism, Single Nucleotide ; Prognosis ; Survival Rate ; Young Adult ; },
abstract = {Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.},
}

Adult
Aged
Aged, 80 and over
Aurora Kinase A/*genetics
Breast Neoplasms/*genetics/mortality/*pathology
Carcinoma, Ductal, Breast/*genetics/mortality/*pathology
Case-Control Studies
Codon
Female
Humans
Iran
Middle Aged
Neoplasm Invasiveness
*Polymorphism, Single Nucleotide
Prognosis
Survival Rate
Young Adult

@article {pmid28934992,
year = {2017},
author = {Plonczak, AM and DiMarco, AN and Dina, R and Gujral, DM and Palazzo, FF},
title = {Breast cancer metastases to the thyroid gland - an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature.},
journal = {Journal of medical case reports},
volume = {11},
number = {1},
pages = {269},
pmid = {28934992},
issn = {1752-1947},
mesh = {Biopsy, Fine-Needle ; Breast Neoplasms/*pathology/therapy ; Carcinoma/diagnosis/*secondary/surgery ; Carcinoma, Papillary/diagnosis ; Chemotherapy, Adjuvant ; Diagnosis, Differential ; Female ; Humans ; Lymph Nodes/*pathology ; Mastectomy ; Middle Aged ; Neck Dissection ; Radiotherapy, Adjuvant ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/diagnosis/*secondary/surgery ; Thyroidectomy ; },
abstract = {BACKGROUND: Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature.

CASE PRESENTATION: A 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy.

CONCLUSIONS: A past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metastases to the thyroid generally indicates poor prognosis, obviating the need of surgery in an already compromised patient. An empirical thyroidectomy should be considered in select patients for local disease control.},
}

Biopsy, Fine-Needle
Breast Neoplasms/*pathology/therapy
Carcinoma/diagnosis/*secondary/surgery
Carcinoma, Papillary/diagnosis
Chemotherapy, Adjuvant
Diagnosis, Differential
Female
Humans
Lymph Nodes/*pathology
Mastectomy
Middle Aged
Neck Dissection
Radiotherapy, Adjuvant
Thyroid Cancer, Papillary
Thyroid Neoplasms/diagnosis/*secondary/surgery
Thyroidectomy

@article {pmid28935545,
year = {2018},
author = {Stires, H and Heckler, MM and Fu, X and Li, Z and Grasso, CS and Quist, MJ and Lewis, JA and Klimach, U and Zwart, A and Mahajan, A and Győrffy, B and Cavalli, LR and Riggins, RB},
title = {Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.},
journal = {Molecular and cellular endocrinology},
volume = {471},
number = {},
pages = {105-117},
pmid = {28935545},
issn = {1872-8057},
support = {P30 CA051008/CA/NCI NIH HHS/United States ; T32 CA009686/CA/NCI NIH HHS/United States ; U54 CA149147/CA/NCI NIH HHS/United States ; },
mesh = {Breast Neoplasms/genetics/*pathology ; Carcinoma, Lobular/genetics/*pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*drug effects/genetics ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic/drug effects ; Glutamic Acid/metabolism ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Mutation/genetics ; Protein Kinase Inhibitors/pharmacology ; Receptors, Estrogen/metabolism ; Receptors, Metabotropic Glutamate/*metabolism ; *Signal Transduction/drug effects ; Tamoxifen/*pharmacology ; Transcriptome/drug effects/genetics ; Exome Sequencing ; },
abstract = {Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.},
}

Breast Neoplasms/genetics/*pathology
Carcinoma, Lobular/genetics/*pathology
Cell Line, Tumor
Drug Resistance, Neoplasm/*drug effects/genetics
Female
Gene Amplification
Gene Expression Regulation, Neoplastic/drug effects
Glutamic Acid/metabolism
Hepatocyte Nuclear Factor 3-alpha/genetics
Humans
Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism
Mitogen-Activated Protein Kinases/*metabolism
Mutation/genetics
Protein Kinase Inhibitors/pharmacology
Receptors, Estrogen/metabolism
Receptors, Metabotropic Glutamate/*metabolism
*Signal Transduction/drug effects
Tamoxifen/*pharmacology
Transcriptome/drug effects/genetics
Exome Sequencing

@article {pmid28938000,
year = {2017},
author = {Suchanski, J and Tejchman, A and Zacharski, M and Piotrowska, A and Grzegrzolka, J and Chodaczek, G and Nowinska, K and Rys, J and Dziegiel, P and Kieda, C and Ugorski, M},
title = {Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.},
journal = {PloS one},
volume = {12},
number = {9},
pages = {e0184970},
pmid = {28938000},
issn = {1932-6203},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*metabolism/pathology ; Cancer-Associated Fibroblasts/*metabolism/pathology ; Carcinoma, Ductal, Breast/metabolism/pathology ; Cell Line ; Cell Movement/*physiology ; Coculture Techniques ; Disease Progression ; Endothelial Cells/*metabolism/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Glycoproteins/genetics/*metabolism ; Middle Aged ; Neoplasm Invasiveness/physiopathology ; RNA, Messenger/metabolism ; Podoplanin ; },
abstract = {In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such podoplanin-mediated effects can affect tube formation by endothelial cells and participate in their pathological properties in the tumor context. Our experimental data were supported by clinical studies. First, when IDC and DCIS were analyzed by immunohistochemistry according to the presence of podoplanin-expressing cells, the numbers of cancer-associated fibroblasts with high expression of this glycoprotein were significantly higher in IDC than in DCIS cases. Second, using immunofluorescence, the co-localization of PDPN-positive CAFs with blood vessels stained with antibody directed against CD34 was observed in tumor stroma of IDC samples.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/*metabolism/pathology
Cancer-Associated Fibroblasts/*metabolism/pathology
Carcinoma, Ductal, Breast/metabolism/pathology
Cell Line
Cell Movement/*physiology
Coculture Techniques
Disease Progression
Endothelial Cells/*metabolism/pathology
Female
Gene Expression Regulation, Neoplastic
Humans
Membrane Glycoproteins/genetics/*metabolism
Middle Aged
Neoplasm Invasiveness/physiopathology
RNA, Messenger/metabolism
Podoplanin

@article {pmid28942323,
year = {2018},
author = {Nawroth, PP and Bendszus, M and Pham, M and Jende, J and Heiland, S and Ries, S and Schumann, C and Schmelz, M and Schuh-Hofer, S and Treede, RD and Kuner, R and Oikonomou, D and Groener, JB and Kopf, S},
title = {The Quest for more Research on Painful Diabetic Neuropathy.},
journal = {Neuroscience},
volume = {387},
number = {},
pages = {28-37},
doi = {10.1016/j.neuroscience.2017.09.023},
pmid = {28942323},
issn = {1873-7544},
mesh = {Animals ; *Biomedical Research ; Diabetic Neuropathies/*complications/diagnosis/drug therapy ; Disease Progression ; Humans ; Pain/*complications ; },
abstract = {A 62-year-old diabetologist diagnosed himself to have diabetes type-2, with an HbA1c of 9.5. Five months after lifestyle intervention and a multi-drug approach, HbA1c was 6.3, systolic blood pressure was below 135mmHg and BMI reduced to 27. But he suffered from severe painful diabetic neuropathy. Therefore he decided to visit his friend, a famous neuroscientist at an even more famous university. He asked him several plain questions: 1. What is the natural course of painful diabetic neuropathy? 2. Why do I have, despite almost normalizing HbA1c, more problems than before? 3. Are you sure my problems are due to diabetes or should we do a nerve biopsy? 4. Are there imaging techniques helpful for the diagnosis of this diabetic complication, starting in the distal nerve endings of the foot and slowly moving ahead? 5. Can you suggest any drug, specific and effective, for relieving painful diabetic neuropathy? This review will use the experts' answers to the questions of the diabetologist, not only to give a summary of the current knowledge, but even more to highlight areas of research needed for improving the fate of patients with painful diabetic neuropathy. Based on the unknowns, which exceed the knowns in diabetic neuropathy, a quest for more public support of research is made.},
}

Animals
*Biomedical Research
Diabetic Neuropathies/*complications/diagnosis/drug therapy
Disease Progression
Humans
Pain/*complications

@article {pmid28954989,
year = {2017},
author = {Nozoe, T and Nozoe, E and Kono, M and Ohga, T and Ezaki, T},
title = {Further evidence to demonstrate the significance of serum appearance of anti-p53 antibody as a marker for progressive potential in invasive ductal carcinoma of the breast.},
journal = {The journal of medical investigation : JMI},
volume = {64},
number = {3.4},
pages = {241-244},
doi = {10.2152/jmi.64.241},
pmid = {28954989},
issn = {1349-6867},
mesh = {Adult ; Aged ; Antibodies/*blood ; Biomarkers, Tumor/blood ; Breast Neoplasms/blood/*pathology ; Carcinoma, Ductal, Breast/blood/*pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Tumor Suppressor Protein p53/*immunology ; },
abstract = {BACKGROUND: Serum appearance of anti-p53 antibody (p53Ab) has been reported as an indicator for progressive potential of human tumor tumors including breast cancer. But its significance in breast cancer has not been discussed fully.

METHODS: Relationship between serum appearance of p53Abs and representative data accounting for progressive potential in breast cancer, nuclear grade (NG), triple negative cancer, and the cumulative score based on these two data (TGS) was investigated among 129 women with invasive ductal carcinoma (IDC) of the breast, who had been treated with surgical resection.

RESULTS: There was a significant correlation between appearance of p53Abs and recurrence of the tumors (P = 0.035). Significant correlation of serum appearance of p53Abs with negative expression of ER (P = 0.011), the proportion of TNBC (P = 0.013), NG (P = 0.017), and TGS (P = 0.0005).

CONCLUSIONS: Preoperative serum appearance of p53Abs can be correlated with pathological nuclear grade, incidence of triple negative breast cancer, and TGS. These results might demonstrate more powerful significance of serum appearance of p53Abs as an indicator of progressive potential in IDC of the breast. J. Med. Invest. 64: 241-244, August, 2017.},
}

Adult
Aged
Antibodies/*blood
Biomarkers, Tumor/blood
Breast Neoplasms/blood/*pathology
Carcinoma, Ductal, Breast/blood/*pathology
Disease Progression
Female
Humans
Middle Aged
Neoplasm Recurrence, Local
Tumor Suppressor Protein p53/*immunology

@article {pmid28967088,
year = {2017},
author = {Cavalieri, S and Stathis, A and Fabbri, A and Sonzogni, A and Perrone, F and Tamborini, E and Pelosi, G and de Braud, F and Platania, M},
title = {Uncommon somatic mutations in metastatic NUT midline carcinoma.},
journal = {Tumori},
volume = {103},
number = {Suppl. 1},
pages = {e5-e8},
doi = {10.5301/tj.5000685},
pmid = {28967088},
issn = {2038-2529},
mesh = {Adult ; Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Carcinoma, Ductal, Breast/*genetics/secondary ; DCC Receptor/genetics ; DNA-Binding Proteins/genetics ; Fatal Outcome ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; *Mutation ; Neoplasm Proteins ; Nuclear Proteins/*genetics ; Oncogene Proteins/*genetics ; Phosphoproteins/genetics ; RNA Splicing Factors/genetics ; },
abstract = {INTRODUCTION:: NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT.

CASE PRESENTATION:: We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast. After 6 months of follow-up a lung nodule appeared. A biopsy showed an adenocarcinoma fetal type/lung blastoma, so a left inferior lobectomy was performed: NMC harboring BRD4-NUT rearrangement was diagnosed. After 9 months of follow-up, bone and soft tissue metastases occurred, so the patient was given radiotherapy. Next-generation sequencing technology identified somatic mutations in deleted in colorectal cancer (DCC), mixed lineage leukemia protein 3 (MLL3), and splicing factor 3B subunit 1 (SF3B1) genes in NMC cells from both primitive cancer and metastases. The patient was treated with the experimental BRD4 inhibitor for 10 months, until the disease progressed to the lung and bone. After spinal cord compression, the patient was offered palliative radiotherapy to bone and eventually died aged 39 years.

CONCLUSIONS:: To the best of our knowledge, our case is the first DCC, MLL3, and SF3B1 mutated NUT midline carcinoma reported in the literature. If these mutations were confirmed to play a role in this neoplasm, clinical trials analyzing targeted therapies should be considered, eg. colorectal cancer-like chemotherapies for DCC mutations, hypomethylating agents for MLL3 mutations or SF3B1 inhibitors in case of specific somatic mutations.},
}

Adult
Biomarkers, Tumor/*genetics
Breast Neoplasms/*genetics/pathology
Carcinoma, Ductal, Breast/*genetics/secondary
DCC Receptor/genetics
DNA-Binding Proteins/genetics
Fatal Outcome
Female
High-Throughput Nucleotide Sequencing
Humans
*Mutation
Neoplasm Proteins
Nuclear Proteins/*genetics
Oncogene Proteins/*genetics
Phosphoproteins/genetics
RNA Splicing Factors/genetics

@article {pmid28982860,
year = {2017},
author = {Grzegrzolka, J and Wojtyra, P and Biala, M and Piotrowska, A and Gomulkiewicz, A and Rys, J and Podhorska-Okolow, M and Dziegiel, P},
title = {Correlation Between Expression of Twist and Podoplanin in Ductal Breast Carcinoma.},
journal = {Anticancer research},
volume = {37},
number = {10},
pages = {5485-5493},
doi = {10.21873/anticanres.11978},
pmid = {28982860},
issn = {1791-7530},
mesh = {Biomarkers, Tumor/*analysis/genetics ; Breast Neoplasms/*chemistry/genetics/mortality/surgery ; Carcinoma, Ductal, Breast/*chemistry/genetics/mortality/surgery ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Membrane Glycoproteins/*analysis/genetics ; Middle Aged ; Nuclear Proteins/*analysis/genetics ; Proportional Hazards Models ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Stromal Cells/chemistry/pathology ; Time Factors ; Treatment Outcome ; Twist-Related Protein 1/*analysis/genetics ; Up-Regulation ; Podoplanin ; },
abstract = {BACKGROUND/AIM: As a result of activation of transcription factors engaged in epithelial-mesenchymal transition (EMT), such as Twist, inhibition of epithelial markers and an increased expression of mesenchymal markers are observed. One of the specific markers of cancer-associated fibroblasts is podoplanin (PDPN) - a mucin-type membrane glycoprotein. The aim of this work was to study the localisation and intensity of expression of Twist and PDPN on the mRNA and protein level in cases of invasive ductal breast carcinoma (IDC), and its association with patients' clinico-pathological data.

MATERIALS AND METHODS: The study included archival material in a form of 80 paraffin IDC blocks and 11 IDC fragments frozen in liquid nitrogen. Immunohistochemical expression of Twist and PDPN was evaluated using light microscope and semiquantitative scale for evaluation of nuclear expression or immunoreactive scale (IRS) for evaluation of cytoplasmic expression. Material was isolated from frozen IDC fragments using laser micro-dissection (from cancer and stromal cells, separately) and was used to perform real-time PCR.

RESULTS: Twist expression was higher in stromal cells in comparison to cancer cells. Analysis of patients' survival rate showed, that higher expression of Twist in cancer cells was associated with shorter overall survival time and shorter event-free survival time. The expression of PDPN was also higher in stromal cells in comparison with cancer cells. In addition, positive correlation was observed between expression of Twist and PDPN in stromal cells of IDC (r=0.267; p<0.05).

CONCLUSION: The relationship between the higher expression of Twist in both cancer and stromal cells and shorter patients' survival indicates Twist as a potential useful prognostic marker in IDC. Positive correlation of Twist and PDPN expression may indicate the role of PDPN in EMT in IDC.},
}

Biomarkers, Tumor/*analysis/genetics
Breast Neoplasms/*chemistry/genetics/mortality/surgery
Carcinoma, Ductal, Breast/*chemistry/genetics/mortality/surgery
Disease-Free Survival
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Membrane Glycoproteins/*analysis/genetics
Middle Aged
Nuclear Proteins/*analysis/genetics
Proportional Hazards Models
RNA, Messenger/genetics
Real-Time Polymerase Chain Reaction
Stromal Cells/chemistry/pathology
Time Factors
Treatment Outcome
Twist-Related Protein 1/*analysis/genetics
Up-Regulation
Podoplanin

@article {pmid28993866,
year = {2018},
author = {Stuebs, F and Heidemann, S and Caliebe, A and Mundhenke, C and Arnold, N},
title = {CDH1 mutation screen in a BRCA1/2-negative familial breast-/ovarian cancer cohort.},
journal = {Archives of gynecology and obstetrics},
volume = {297},
number = {1},
pages = {147-152},
doi = {10.1007/s00404-017-4551-1},
pmid = {28993866},
issn = {1432-0711},
mesh = {Adult ; Antigens, CD/*metabolism ; BRCA1 Protein/*metabolism ; BRCA2 Protein/*metabolism ; Breast Neoplasms/*genetics/pathology ; Cadherins/*metabolism ; Cohort Studies ; Early Detection of Cancer ; Female ; Genetic Predisposition to Disease ; Humans ; Mutation ; Ovarian Neoplasms/*genetics/pathology ; },
abstract = {PURPOSE: Mutations in the CDH1 gene are linked both to diffuse gastric cancer and invasive lobular carcinoma (ILC). A high mutation rate is found in families fulfilling the diagnostic criteria for hereditary diffuse gastric cancer. Aim of this study was to clarify whether or not there is a significant contribution of CDH1 mutations in hereditary breast-/ovarian cancer (HBOC).

METHODS: Ninety-seven unrelated probands fulfilling the diagnostic criteria for HBOC (96 affected, 1 unaffected) but tested negative for pathogenic BRCA1/2 mutations were screened for CDH1 mutations by denaturing high performance liquid chromatography (DHPLC) and subsequent Sanger sequencing of suspicious and positive DHPLC results.

RESULTS: In total, we found two potentially pathogenic CDH1 alterations, c.1774G > A, pAla592Thr, and c.2512 A > G, p.Ser838Gly, classified as variants of unknown significance according to ClinVar. In addition, we detected a high number of known CDH1 polymorphisms (n = 62), some of them more frequent in patients with lobular (55%) than in those with invasive ductal carcinoma (27%).

CONCLUSION: Although none of the probands studied carried a clearly pathogenic CDH1 mutation, CDH1 could be considered a potential breast cancer gene, esp. for ILC worth including it in the NGS (next generation sequencing) HBOC panel.},
}

Adult
Antigens, CD/*metabolism
BRCA1 Protein/*metabolism
BRCA2 Protein/*metabolism
Breast Neoplasms/*genetics/pathology
Cadherins/*metabolism
Cohort Studies
Early Detection of Cancer
Female
Genetic Predisposition to Disease
Humans
Mutation
Ovarian Neoplasms/*genetics/pathology

@article {pmid29043464,
year = {2018},
author = {Mordang, JJ and Gubern-Mérida, A and Bria, A and Tortorella, F and Mann, RM and Broeders, MJM and den Heeten, GJ and Karssemeijer, N},
title = {The importance of early detection of calcifications associated with breast cancer in screening.},
journal = {Breast cancer research and treatment},
volume = {167},
number = {2},
pages = {451-458},
pmid = {29043464},
issn = {1573-7217},
support = {KUN 2012-5577//KWF Kankerbestrijding/International ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*complications/pathology ; Calcinosis/complications/*diagnosis/pathology ; *Early Diagnosis ; Female ; Humans ; Mammography ; Mass Screening ; Middle Aged ; },
abstract = {PURPOSE: The aim of this study was to assess how often women with undetected calcifications in prior screening mammograms are subsequently diagnosed with invasive cancer.

METHODS: From a screening cohort of 63,895 women, exams were collected from 59,690 women without any abnormalities, 744 women with a screen-detected cancer and a prior negative exam, 781 women with a false positive exam based on calcifications, and 413 women with an interval cancer. A radiologist identified cancer-related calcifications, selected by a computer-aided detection system, on mammograms taken prior to screen-detected or interval cancer diagnoses. Using this ground truth and the pathology reports, the sensitivity for calcification detection and the proportion of lesions with visible calcifications that developed into invasive cancer were determined.

RESULTS: The screening sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of 68.4% (n = 177) of cancer-related calcifications that could have been detected earlier were associated with invasive cancer when diagnosed.

CONCLUSIONS: Screening sensitivity for detection of malignant calcifications is low. Improving the detection of these early signs of cancer is important, because the majority of lesions with detectable calcifications that are not recalled immediately but detected as interval cancer or in the next screening round are invasive at the time of diagnosis.},
}

Adult
Aged
Breast Neoplasms/*complications/pathology
Calcinosis/complications/*diagnosis/pathology
*Early Diagnosis
Female
Humans
Mammography
Mass Screening
Middle Aged

@article {pmid29045292,
year = {2018},
author = {Bennett, JA and Young, RH and Chuang, AY and Lerwill, MF},
title = {Ovarian Metastases of Breast Cancers With Signet Ring Cells: A Report of 17 Cases Including 14 Krukenberg Tumors.},
journal = {International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists},
volume = {37},
number = {6},
pages = {507-515},
doi = {10.1097/PGP.0000000000000462},
pmid = {29045292},
issn = {1538-7151},
mesh = {Adenocarcinoma/*secondary ; Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*secondary ; Carcinoma, Signet Ring Cell/*secondary ; Female ; Humans ; Krukenberg Tumor/*secondary ; Middle Aged ; Ovarian Neoplasms/*secondary ; },
abstract = {Krukenberg tumor, defined as metastatic adenocarcinoma to the ovary containing at least 10% signet ring cells, usually arises from the stomach but can also originate from other sites. We reviewed 17 metastatic breast carcinomas to the ovary with signet ring cells to potentially identify features indicative of mammary origin as opposed to other possible primary sites. The patients ranged from 41 to 76 (mean, 53.6) yr. Fourteen had a prior history of invasive breast carcinoma (invasive ductal carcinoma, 4; invasive lobular carcinoma, 3; adenocarcinoma not otherwise specified, 3; carcinoma with ductal and lobular features, 2; and unspecified carcinoma, 2) and metastases were identified 2 to 284 (mean, 79) mo after the original diagnosis. Three patients had no known history of invasive breast carcinoma: 1 was subsequently diagnosed with invasive lobular carcinoma, 1 had suspicious bilateral breast masses identified on imaging, and 1 was lost to follow-up. Bilateral ovarian metastases were present in 87%, and the tumors ranged from 3.8 to 19 (mean, 8) cm. Microscopically the ovarian architecture was effaced in 71% by discrete tumor lobules separated by striking edema. The tumors exhibited a variety of histologic patterns: nests were most common (88%), followed by cords (82%), diffuse sheets (82%), single cells (71%), small clusters (41%), glands (29%), and follicle-like cysts (12%). Signet ring cells comprised 2% to 70% (mean, 33%) of the tumors, with 14 cases meeting the criteria for Krukenberg tumor. Signet ring cells were most frequently observed within diffuse sheets (71%) and cords (65%). Tumor cells arranged in nests, cords, and diffuse sheets are typical of Krukenberg tumor of breast origin, and the patterns recapitulate those seen in primary breast carcinomas. Features characteristic of gastrointestinal origin, such as extracellular mucin, intestinal-type glands, dirty necrosis, microcysts, and goblet cell carcinoid-like foci, were absent. The overall morphologic picture in cases of ovarian spread of breast cancer with signet ring cells is usually strongly suggestive of mammary origin. The diagnosis can be further supported by the clinical history and immunohistochemical evaluation.},
}

Adenocarcinoma/*secondary
Adult
Aged
Breast Neoplasms/*pathology
Carcinoma, Ductal, Breast/*secondary
Carcinoma, Signet Ring Cell/*secondary
Female
Humans
Krukenberg Tumor/*secondary
Middle Aged
Ovarian Neoplasms/*secondary

@article {pmid29052527,
year = {2017},
author = {Chen, HR and Wu, YT and Yu, QB and Yang, YY and Wei, YX and Li, HY and Wu, KN and Kong, LQ},
title = {Negative genic switch of HER-2 in the primary tumor instead of the synchronous metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary HER2-positive breast cancer.},
journal = {World journal of surgical oncology},
volume = {15},
number = {1},
pages = {189},
pmid = {29052527},
issn = {1477-7819},
mesh = {Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Axilla ; Biopsy, Large-Core Needle ; Breast Neoplasms/*genetics/pathology/therapy ; Carcinoma, Ductal, Breast/*genetics/pathology/secondary/therapy ; Chemoradiotherapy, Adjuvant ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lymph Nodes/*pathology/surgery ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoadjuvant Therapy/*methods ; Erb-b2 Receptor Tyrosine Kinases/antagonists & inhibitors/*genetics ; Trastuzumab/therapeutic use ; },
abstract = {BACKGROUND: A few retrospective studies have indicated that neoadjuvant chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary tumor. Little is known about the status of HER-2 gene of the synchronous nodal metastases when that of the residual tumor undergoes negative conversion in a neoadjuvant setting.

CASE PRESENTATION: We describe a female patient with left breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and amplified HER-2 gene determined by fluorescence in situ hybridization (FISH). Then, the patient underwent 4 cycles of anthracycline- and taxane-based NAC and subsequent left modified radical mastectomy. Postoperative pathology showed invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the residual tumor of the breast specimen. Due to the negative genic switch of HER2 after NAC, the patient rejected to accept trastuzumab. Under the patient's consent, the synchronous nodal lesions were further investigated and showed HER2 IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to accept adjuvant trastuzumab treatment every 3 weeks for 1 year.

CONCLUSIONS: We propose further assessment of HER2 gene in the synchronous nodal metastases, especially when negative genic switch of HER-2 occurs in the primary tumor after NAC in order to tailor the systemic regimens for breast cancer patients.},
}

Antineoplastic Agents, Immunological/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Axilla
Biopsy, Large-Core Needle
Breast Neoplasms/*genetics/pathology/therapy
Carcinoma, Ductal, Breast/*genetics/pathology/secondary/therapy
Chemoradiotherapy, Adjuvant
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymph Nodes/*pathology/surgery
Lymphatic Metastasis
Mastectomy
Middle Aged
Neoadjuvant Therapy/*methods
Erb-b2 Receptor Tyrosine Kinases/antagonists & inhibitors/*genetics
Trastuzumab/therapeutic use

@article {pmid29065116,
year = {2017},
author = {Picillo, M and Pivonello, R and Santangelo, G and Pivonello, C and Savastano, R and Auriemma, R and Amboni, M and Scannapieco, S and Pierro, A and Colao, A and Barone, P and Pellecchia, MT},
title = {Serum IGF-1 is associated with cognitive functions in early, drug-naïve Parkinson's disease.},
journal = {PloS one},
volume = {12},
number = {10},
pages = {e0186508},
pmid = {29065116},
issn = {1932-6203},
mesh = {Adult ; Aged ; Aged, 80 and over ; Cognition Disorders/*blood/complications ; Female ; Humans ; Insulin-Like Growth Factor I/*metabolism ; Male ; Middle Aged ; Parkinson Disease/blood/*complications ; },
abstract = {OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) since the early stages and many patients eventually develop dementia. Yet, occurrence of dementia in PD is unpredictable. Evidence supports the hypothesis that insulin-like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to evaluate the relationship between serum IGF-1 levels and neuropsychological scores in a large cohort of drug-naïve PD patients during the earliest stages of the disease.

METHODS: Serum IGF-1 levels were determined in 405 early, drug-naïve PD patients and 191 healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). The association between serum IGF-1 levels and neuropsychological scores was evaluated with linear regression analysis.

RESULTS: IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile was a predictor of lower performances at the Semantic Fluency task (β = -3.46, 95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (β = -2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test Retention (β = -0.05, 95%CI: -0.09 to -0.009, p = 0.019).

CONCLUSIONS: Lower serum IGF-1 levels are associated to poor performances in cognitive tasks assessing executive function, attention and verbal memory in a large cohort of early PD patients. Follow-up studies are warranted to assess if IGF-1 is related to the development of dementia in PD.},
}

Adult
Aged
Aged, 80 and over
Cognition Disorders/*blood/complications
Female
Humans
Insulin-Like Growth Factor I/*metabolism
Male
Middle Aged
Parkinson Disease/blood/*complications

@article {pmid29069648,
year = {2017},
author = {Huang, R and Han, J and Liang, X and Sun, S and Jiang, Y and Xia, B and Niu, M and Li, D and Zhang, J and Wang, S and Wei, W and Liu, Q and Zheng, W and Zhang, G and Song, Y and Panga, D},
title = {Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer.},
journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology},
volume = {43},
number = {6},
pages = {2212-2225},
doi = {10.1159/000484300},
pmid = {29069648},
issn = {1421-9778},
mesh = {Androgen Receptor Antagonists/*pharmacology/therapeutic use ; Anilides/*pharmacology/therapeutic use ; Animals ; Apoptosis/drug effects ; Breast Neoplasms/drug therapy/mortality/*pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Down-Regulation/drug effects ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Nitriles/*pharmacology/therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, Androgen/chemistry/*genetics/metabolism ; Receptors, Estrogen/*genetics/metabolism ; Signal Transduction/drug effects ; Tosyl Compounds/*pharmacology/therapeutic use ; Transcription, Genetic/*drug effects ; Transplantation, Heterologous ; beta Catenin/genetics/*metabolism ; },
abstract = {BACKGROUND/AIMS: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment.

METHODS: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer.

RESULTS: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer.

CONCLUSION: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.},
}

Androgen Receptor Antagonists/*pharmacology/therapeutic use
Anilides/*pharmacology/therapeutic use
Animals
Apoptosis/drug effects
Breast Neoplasms/drug therapy/mortality/*pathology
Cell Line, Tumor
Cell Proliferation/drug effects
Down-Regulation/drug effects
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Nitriles/*pharmacology/therapeutic use
Prognosis
Proto-Oncogene Proteins c-myc/metabolism
Receptors, Androgen/chemistry/*genetics/metabolism
Receptors, Estrogen/*genetics/metabolism
Signal Transduction/drug effects
Tosyl Compounds/*pharmacology/therapeutic use
Transcription, Genetic/*drug effects
Transplantation, Heterologous
beta Catenin/genetics/*metabolism

@article {pmid29072365,
year = {2017},
author = {Chen, H and Wu, K and Wang, M and Wang, F and Zhang, M and Zhang, P},
title = {Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.},
journal = {Cancer medicine},
volume = {6},
number = {12},
pages = {2775-2786},
pmid = {29072365},
issn = {2045-7634},
mesh = {Biomarkers, Tumor/analysis ; Breast Neoplasms/chemistry/*mortality/pathology/therapy ; Carcinoma, Ductal, Breast/chemistry/*mortality/secondary/therapy ; Carcinoma, Papillary/chemistry/*mortality/secondary/therapy ; Chi-Square Distribution ; Databases, Factual ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Propensity Score ; Proportional Hazards Models ; Receptors, Estrogen/analysis ; Receptors, Progesterone/analysis ; Retrospective Studies ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; },
abstract = {There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation.},
}

Biomarkers, Tumor/analysis
Breast Neoplasms/chemistry/*mortality/pathology/therapy
Carcinoma, Ductal, Breast/chemistry/*mortality/secondary/therapy
Carcinoma, Papillary/chemistry/*mortality/secondary/therapy
Chi-Square Distribution
Databases, Factual
Disease Progression
Disease-Free Survival
Female
Humans
Kaplan-Meier Estimate
Lymphatic Metastasis
Middle Aged
Multivariate Analysis
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Staging
Propensity Score
Proportional Hazards Models
Receptors, Estrogen/analysis
Receptors, Progesterone/analysis
Retrospective Studies
Risk Factors
SEER Program
Time Factors
Treatment Outcome
United States/epidemiology

@article {pmid29076877,
year = {2018},
author = {Skálová, A and Stenman, G and Simpson, RHW and Hellquist, H and Slouka, D and Svoboda, T and Bishop, JA and Hunt, JL and Nibu, KI and Rinaldo, A and Vander Poorten, V and Devaney, KO and Steiner, P and Ferlito, A},
title = {The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas.},
journal = {The American journal of surgical pathology},
volume = {42},
number = {2},
pages = {e11-e27},
doi = {10.1097/PAS.0000000000000980},
pmid = {29076877},
issn = {1532-0979},
mesh = {Biomarkers, Tumor/*genetics ; Biopsy ; Carcinoma/*genetics/pathology/therapy ; Diagnosis, Differential ; Gene Fusion ; Genetic Predisposition to Disease ; Humans ; *Molecular Diagnostic Techniques ; Mutation ; Neoplasm Grading ; Phenotype ; Predictive Value of Tests ; Salivary Gland Neoplasms/*genetics/pathology/therapy ; Translocation, Genetic ; },
abstract = {Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.},
}

Biomarkers, Tumor/*genetics
Biopsy
Carcinoma/*genetics/pathology/therapy
Diagnosis, Differential
Gene Fusion
Genetic Predisposition to Disease
Humans
*Molecular Diagnostic Techniques
Mutation
Neoplasm Grading
Phenotype
Predictive Value of Tests
Salivary Gland Neoplasms/*genetics/pathology/therapy
Translocation, Genetic

@article {pmid29090670,
year = {2018},
author = {Gurzu, S and Banias, L and Bara, T and Feher, I and Bara, T and Jung, I},
title = {The Epithelial-Mesenchymal Transition Pathway in Two Cases with Gastric Metastasis Originating from Breast Carcinoma, One with a Metachronous Primary Gastric Cancer.},
journal = {Recent patents on anti-cancer drug discovery},
volume = {13},
number = {1},
pages = {118-124},
doi = {10.2174/2212798409666171101121108},
pmid = {29090670},
issn = {2212-3970},
mesh = {Aged ; Breast Neoplasms/diagnosis/*metabolism ; Epithelial-Mesenchymal Transition/*physiology ; Female ; Humans ; Neoplasms, Second Primary/diagnosis/*metabolism/secondary ; Stomach Neoplasms/diagnosis/*metabolism/secondary ; },
abstract = {BACKGROUND: Metastases to the stomach are extremely rare and the metastatic pathway is not well understood.

OBJECTIVE: To present two unusual gastric metastases and a review of the literature regarding the pathway of Epithelial Mesenchymal Transition (EMT) in the metastatic cells.

METHOD: The clinicopathological aspects of the two cases were presented in the light of the most recent patents. Data about patents were obtained from the online databases PubMed, World Intellectual Property Organization (WIPO) and Google patents.

RESULTS: In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, β-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed. In the second case, a 67-year-old female with invasive ductal carcinoma of the breast, which benefited from chemotherapy and mastectomy, presented a metachronous gastric adenocarcinoma with collision-type metastatic breast ductal carcinoma. The aggressiveness of the GC cells was induced through the E-cadherin/maspin pathway, while the CD44-related stem-like properties of the tumor cells induced the aggressiveness of ductal carcinoma.

CONCLUSION: In females with breast cancer, a possible metastasis in the stomach should be taken into account. Maspin and VSIG1 are not involved in breast cancer histogenesis. The Wnt/β-catenin signaling is not involved in the lobular carcinoma progression. The CD44/HER2 positivity in ductal carcinoma cells might indicate high risk of distant metastasis and low response to chemotherapy.},
}

Aged
Breast Neoplasms/diagnosis/*metabolism
Epithelial-Mesenchymal Transition/*physiology
Female
Humans
Neoplasms, Second Primary/diagnosis/*metabolism/secondary
Stomach Neoplasms/diagnosis/*metabolism/secondary

@article {pmid29126758,
year = {2017},
author = {Helal, DS and El-Guindy, DM},
title = {Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density.},
journal = {Journal of the Egyptian National Cancer Institute},
volume = {29},
number = {4},
pages = {177-183},
doi = {10.1016/j.jnci.2017.09.002},
pmid = {29126758},
issn = {2589-0409},
mesh = {Adult ; Aged ; Breast Neoplasms/diagnosis/*genetics/*metabolism ; Carcinoma, Ductal, Breast/diagnosis/*genetics/*metabolism ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/genetics/metabolism ; Prognosis ; Protein Transport ; Serpins/*genetics/*metabolism ; Tumor Burden ; },
abstract = {Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.},
}

Adult
Aged
Breast Neoplasms/diagnosis/*genetics/*metabolism
Carcinoma, Ductal, Breast/diagnosis/*genetics/*metabolism
Female
Gene Expression
Humans
Immunohistochemistry
Middle Aged
Neoplasm Grading
Neoplasm Staging
Neovascularization, Pathologic/genetics/metabolism
Prognosis
Protein Transport
Serpins/*genetics/*metabolism
Tumor Burden

@article {pmid29131529,
year = {2017},
author = {Yang, LP and Sun, HF and Zhao, Y and Chen, MT and Zhang, N and Jin, W},
title = {Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.},
journal = {Cancer medicine},
volume = {6},
number = {12},
pages = {2867-2875},
pmid = {29131529},
issn = {2045-7634},
mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Breast Neoplasms/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/*secondary/therapy ; Carcinoma, Lobular/mortality/*secondary/therapy ; Chi-Square Distribution ; Disease Progression ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Staging ; Risk Factors ; SEER Program ; Time Factors ; Treatment Outcome ; United States/epidemiology ; Young Adult ; },
abstract = {The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.},
}

Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Breast Neoplasms/mortality/*pathology/therapy
Carcinoma, Ductal, Breast/mortality/*secondary/therapy
Carcinoma, Lobular/mortality/*secondary/therapy
Chi-Square Distribution
Disease Progression
Disease-Free Survival
Humans
Kaplan-Meier Estimate
Lymphatic Metastasis
Middle Aged
Multivariate Analysis
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Staging
Risk Factors
SEER Program
Time Factors
Treatment Outcome
United States/epidemiology
Young Adult

@article {pmid29142206,
year = {2017},
author = {Wang, CQ and Li, Y and Huang, BF and Zhao, YM and Yuan, H and Guo, D and Su, CM and Hu, GN and Wang, Q and Long, T and Wang, Y and Tang, CH and Li, X},
title = {EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.},
journal = {Scientific reports},
volume = {7},
number = {1},
pages = {15654},
pmid = {29142206},
issn = {2045-2322},
mesh = {Adult ; Aged ; Biomarkers, Tumor/genetics ; Carcinoma, Ductal, Breast/*genetics/pathology ; Carrier Proteins/*genetics ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; ErbB Receptors/genetics ; Female ; Gefitinib/administration & dosage ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Microfilament Proteins/*genetics ; Middle Aged ; *Molecular Targeted Therapy ; Neoplasm Recurrence, Local/drug therapy/genetics/pathology ; Progression-Free Survival ; Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology ; },
abstract = {Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.},
}

Adult
Aged
Biomarkers, Tumor/genetics
Carcinoma, Ductal, Breast/*genetics/pathology
Carrier Proteins/*genetics
Cell Movement/drug effects
Cell Proliferation/drug effects
ErbB Receptors/genetics
Female
Gefitinib/administration & dosage
Gene Expression Regulation, Neoplastic/drug effects
Humans
Microfilament Proteins/*genetics
Middle Aged
*Molecular Targeted Therapy
Neoplasm Recurrence, Local/drug therapy/genetics/pathology
Progression-Free Survival
Triple Negative Breast Neoplasms/drug therapy/*genetics/pathology

@article {pmid29146271,
year = {2018},
author = {Co, M and Kwong, A and Shek, T},
title = {Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies - A 10-year retrospective study and review of the literature.},
journal = {International journal of surgery (London, England)},
volume = {49},
number = {},
pages = {27-31},
doi = {10.1016/j.ijsu.2017.11.005},
pmid = {29146271},
issn = {1743-9159},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biopsy, Large-Core Needle/methods/*statistics & numerical data ; Breast/diagnostic imaging/pathology ; Breast Neoplasms/*diagnosis/pathology ; Carcinoma in Situ/pathology ; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology ; Carcinoma, Lobular/pathology ; Diagnostic Errors ; Female ; Humans ; Mammography ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult ; },
abstract = {INTRODUCTION: Due to the possibility of underestimation, surgical excision is usually offered to patients with atypical ductal hyperplasia (ADH) diagnosed with core needle biopsy (CNB). Here we review the 10-year data of patients with ADH diagnosed by CNB, aiming to identify the factors associated with under-diagnosis.

METHODS: Retrospective review of database from 1st Jan 2005 to 31st Dec 2014 was performed; patients with ADH diagnosed by CNB were identified. Diagnosis upgrade rate and its risk factors were evaluated.

RESULTS: 104 patients were found to have ADH on CNB, 101 patients received excisional biopsy while 3 patients refused operation. 34 patients had ductal carcinoma in situ (DCIS) after excision, 6 had invasive ductal carcinoma, 1 had lobular carcinoma in situ and 1 had angiosarcoma. CNB under-diagnosed up to 41.6% of malignant lesions. Breast mass on presentation and suspicious mammograms (BIRADS ≥ 4) are associated with diagnosis upgrade (P = 0.0005, 0.0001). Literature review of 39 studies between 1997 and 2017 revealed 3125 excision procedures performed for ADH diagnosed by CNB, the pooled median diagnosis upgrade rate was 25% (Range 4-54%).

CONCLUSION: We recommend excision in all patients with ADH diagnosed by CNB, especially in patients with suspicious mammographic features.},
}

Adult
Aged
Aged, 80 and over
Biopsy, Large-Core Needle/methods/*statistics & numerical data
Breast/diagnostic imaging/pathology
Breast Neoplasms/*diagnosis/pathology
Carcinoma in Situ/pathology
Carcinoma, Intraductal, Noninfiltrating/*diagnosis/pathology
Carcinoma, Lobular/pathology
Diagnostic Errors
Female
Humans
Mammography
Middle Aged
Retrospective Studies
Risk Factors
Young Adult

@article {pmid29154888,
year = {2017},
author = {Hou, N and Wen, Y and Yuan, X and Xu, H and Wang, X and Li, F and Ye, B},
title = {Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy.},
journal = {Experimental and molecular pathology},
volume = {103},
number = {3},
pages = {267-275},
pmid = {29154888},
issn = {1096-0945},
support = {R01 HL072166/HL/NHLBI NIH HHS/United States ; R01 HL111480/HL/NHLBI NIH HHS/United States ; R01 HL122793/HL/NHLBI NIH HHS/United States ; },
mesh = {Acyltransferases ; Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Cardiomyopathies/genetics/pathology ; Cardiomyopathy, Dilated/*genetics/pathology ; DNA-Binding Proteins/*genetics ; Humans ; Mice ; Muscular Dystrophies/genetics/pathology ; Myocardial Ischemia/*genetics/pathology ; Nuclear Proteins/*genetics ; Phosphoproteins/*genetics ; Signal Transduction/genetics ; TEA Domain Transcription Factors ; Transcription Factors/*genetics ; YAP-Signaling Proteins ; },
abstract = {Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES). Our results demonstrated that Yap1, Taz, and Tead1 were significantly increased in failing human and DES hearts compared with the non-failing controls (NFH) or wild type (WT) mouse hearts at both mRNA and protein levels. Interestingly, adult human and mouse hearts had more Taz than Yap1 by mRNA and protein expression and their increases in diseased hearts were proportional and did not change Yap1/Taz ratio. Yap1, Taz, and Tead1 were accumulated in the nuclear fraction and cardiomyocyte nuclei of diseased hearts. The ratio of Yap1 phosphorylated at serine 127 (human) or serine 112 (mouse) to the total Yap1 (pYap1/Yap1) was significantly lower in the nuclear fraction of diseased hearts than that in normal controls. More importantly, Hippo downstream targets Ankrd1, Ctgf, and Cyr61 were transcriptionally elevated in the diseased hearts. These results suggest that Yap1/Taz signaling is activated in human and mouse dysfunctional hearts. Further investigation with relevant animal models will determine whether this pathway is a potential target for preventing and reversing abnormal remodeling during the progression of different cardiac disorders.},
}

Acyltransferases
Adaptor Proteins, Signal Transducing/*genetics
Animals
Cardiomyopathies/genetics/pathology
Cardiomyopathy, Dilated/*genetics/pathology
DNA-Binding Proteins/*genetics
Humans
Mice
Muscular Dystrophies/genetics/pathology
Myocardial Ischemia/*genetics/pathology
Nuclear Proteins/*genetics
Phosphoproteins/*genetics
Signal Transduction/genetics
TEA Domain Transcription Factors
Transcription Factors/*genetics
YAP-Signaling Proteins

@article {pmid29155474,
year = {2018},
author = {Gilboa, Y and Frenkel, TI and Schlesinger, Y and Rousseau, S and Hamiel, D and Achiron, R and Perlman, S},
title = {Visual biofeedback using transperineal ultrasound in second stage of labor.},
journal = {Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology},
volume = {52},
number = {1},
pages = {91-96},
doi = {10.1002/uog.18962},
pmid = {29155474},
issn = {1469-0705},
mesh = {Adult ; *Biofeedback, Psychology ; Delivery, Obstetric/*methods ; Female ; Head/*diagnostic imaging/embryology ; Humans ; Infant, Newborn ; Labor Stage, Second/*physiology ; Perineum/*diagnostic imaging ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Self Report ; *Ultrasonography/methods ; },
abstract = {OBJECTIVE: To assess the obstetric and psychological effects of visual biofeedback by transperineal ultrasound (TPU) during the second stage of labor.

METHODS: This was a prospective, single-center observational study of low-risk nulliparous women with epidural analgesia undergoing vaginal delivery. Visual biofeedback using TPU was provided to 26 women during the second stage of labor. Pushing efficacy was assessed by the change in the angle of progression (AoP) at rest and during pushing efforts, before and after biofeedback. Obstetric outcomes included incidence of perineal tearing, mode of delivery and length of second stage of labor. Psychological outcomes were assessed by self-reported measures obtained during the postnatal hospital stay and included measures of perceived control and maternal satisfaction with childbirth, as well as level of maternal feelings of connectedness with the newborn. Obstetric and psychological results were compared with those of a control group of 69 women who received standard obstetric coaching from midwives.

RESULTS: Pushing efficacy increased significantly following visual biofeedback by TPU (P = 0.01), as indicated by a significantly lower delta AoP before (mean, 22.2° (95% CI, 13.9-31.7°)) compared with after (mean, 35.2° (95% CI, 25.9-45.3°)) biofeedback. A significant association was found between visual biofeedback and an intact perineum following delivery (P = 0.03). No significant differences were found between the two groups with regard to mode of delivery or length of the second stage. Feelings of maternal connectedness with the newborn were significantly stronger (P = 0.003) in women who received visual biofeedback than in those who did not. However, perceived control during childbirth and maternal satisfaction with childbirth did not differ significantly between the biofeedback and control groups.

CONCLUSIONS: This pilot study suggests that biofeedback using TPU may serve as a complementary tool to coached maternal pushing during the second stage of labor, with obstetric as well as psychological benefits. Further studies are required to confirm our findings and define the optimal duration of the intervention. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.},
}

Adult
*Biofeedback, Psychology
Delivery, Obstetric/*methods
Female
Head/*diagnostic imaging/embryology
Humans
Infant, Newborn
Labor Stage, Second/*physiology
Perineum/*diagnostic imaging
Pregnancy
Pregnancy Outcome
Prospective Studies
Self Report
*Ultrasonography/methods

@article {pmid29164828,
year = {2019},
author = {Koren, D and Rothschild-Yakar, L and Lacoua, L and Brunstein-Klomek, A and Zelezniak, A and Parnas, J and Shahar, G},
title = {Attenuated psychosis and basic self-disturbance as risk factors for depression and suicidal ideation/behaviour in community-dwelling adolescents.},
journal = {Early intervention in psychiatry},
volume = {13},
number = {3},
pages = {532-538},
doi = {10.1111/eip.12516},
pmid = {29164828},
issn = {1751-7893},
support = {//University of Haifa/International ; //Israel Science Foundation/International ; },
mesh = {Adolescent ; Depressive Disorder/*diagnosis/psychology ; Major Depressive Disorder/diagnosis/psychology ; *Ego ; Female ; Humans ; Independent Living/psychology ; Male ; Pilot Projects ; Prodromal Symptoms ; Psychotic Disorders/*diagnosis/psychology ; Risk Factors ; Self-Injurious Behavior/diagnosis/psychology ; *Suicidal Ideation ; Suicide, Attempted/*psychology ; Surveys and Questionnaires ; },
abstract = {BACKGROUND AND AIMS: Adolescents at clinical high risk (CHR) for psychosis, as defined by the presence of attenuated psychosis symptoms (APS), exhibit increased levels of suicidal ideation and behaviour. However, no research thus far has examined the link between basic self-disturbances (SDs), an established marker for CHR, and suicidality/self-harm in this population. The goal of this pilot study was to assess the association between SD, depression and suicidal ideation and behaviour among non-help-seeking adolescents from the community.

METHOD: A total of 100 community-dwelling adolescents (age range: 13-16) were assessed using the Examination of Anomalous Self-experience, Prodromal Questionnaire, Structured Interview for Prodromal Syndromes, Mood and Anxiety Symptom Questionnaire and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The K-SADS was used to derive a binary diagnosis of unipolar depression, as well as to measure suicidal ideation and behaviour and self-harm.

RESULTS: In a multiple regression analysis, SD accounted for variance in depressive symptoms and suicidality/self-harm over and above that accounted for by APS. Moreover, SD accounted for variance in suicidality/self-harm over and above that accounted for by depression symptoms.

CONCLUSIONS: These pilot results suggest that SD might be a unique dimension of vulnerability to depression and suicidality/self-harm in adolescence. Also, they encourage assessment of SD as part of a suicide risk assessment, particularly in the context of risk for subsequent psychosis.},
}

Adolescent
Depressive Disorder/*diagnosis/psychology
Major Depressive Disorder/diagnosis/psychology
*Ego
Female
Humans
Independent Living/psychology
Male
Pilot Projects
Prodromal Symptoms
Psychotic Disorders/*diagnosis/psychology
Risk Factors
Self-Injurious Behavior/diagnosis/psychology
*Suicidal Ideation
Suicide, Attempted/*psychology
Surveys and Questionnaires

@article {pmid29189723,
year = {2017},
author = {Giroud, M and Scheideler, M},
title = {Long Non-Coding RNAs in Metabolic Organs and Energy Homeostasis.},
journal = {International journal of molecular sciences},
volume = {18},
number = {12},
pages = {},
pmid = {29189723},
issn = {1422-0067},
mesh = {Adipose Tissue/metabolism ; Animals ; Energy Metabolism/genetics/physiology ; Gene Expression Regulation ; Homeostasis ; Humans ; Muscle, Skeletal/metabolism ; Pancreas/metabolism ; RNA, Long Noncoding/genetics/*metabolism ; },
abstract = {Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization. lncRNAs are transcriptional regulators adding an additional regulatory layer in biological processes and pathophysiological conditions. Here, we review lncRNAs affecting metabolic organs with a focus on the liver, pancreas, skeletal muscle, cardiac muscle, brain, and adipose organ. In addition, we will discuss the impact of lncRNAs on metabolic diseases such as obesity and diabetes. In contrast to the substantial number of lncRNA loci in the human genome, the functionally characterized lncRNAs are just the tip of the iceberg. So far, our knowledge concerning lncRNAs in energy homeostasis is still in its infancy, meaning that the rest of the iceberg is a treasure chest yet to be discovered.},
}

Adipose Tissue/metabolism
Animals
Energy Metabolism/genetics/physiology
Gene Expression Regulation
Homeostasis
Humans
Muscle, Skeletal/metabolism
Pancreas/metabolism
RNA, Long Noncoding/genetics/*metabolism

@article {pmid29195137,
year = {2018},
author = {Rezende, F and Moll, F and Walter, M and Helfinger, V and Hahner, F and Janetzko, P and Ringel, C and Weigert, A and Fleming, I and Weissmann, N and Kuenne, C and Looso, M and Rieger, MA and Nawroth, P and Fleming, T and Brandes, RP and Schröder, K},
title = {The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.},
journal = {Redox biology},
volume = {15},
number = {},
pages = {12-21},
pmid = {29195137},
issn = {2213-2317},
mesh = {Adaptor Proteins, Signal Transducing ; Animals ; Aorta/metabolism/pathology ; Diabetes Mellitus, Experimental/*genetics/metabolism/pathology ; Endothelial Cells/metabolism ; Gene Expression ; Humans ; Lymphocytes/metabolism/pathology ; Mice ; Mice, Knockout ; NADP/metabolism ; NADPH Oxidases/*genetics/metabolism ; Protein Binding ; Proteins/*genetics ; Reactive Oxygen Species/metabolism ; },
abstract = {AIM: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.

RESULTS: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.

INNOVATION AND CONCLUSION: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.},
}

Adaptor Proteins, Signal Transducing
Animals
Aorta/metabolism/pathology
Diabetes Mellitus, Experimental/*genetics/metabolism/pathology
Endothelial Cells/metabolism
Gene Expression
Humans
Lymphocytes/metabolism/pathology
Mice
Mice, Knockout
NADP/metabolism
NADPH Oxidases/*genetics/metabolism
Protein Binding
Proteins/*genetics
Reactive Oxygen Species/metabolism

@article {pmid29206714,
year = {2018},
author = {Khanlari, M and Schally, AV and Block, NL and Nadji, M},
title = {Expression of GHRH-R, a Potentially Targetable Biomarker, in Triple-negative Breast Cancer.},
journal = {Applied immunohistochemistry & molecular morphology : AIMM},
volume = {26},
number = {1},
pages = {1-5},
doi = {10.1097/PAI.0000000000000622},
pmid = {29206714},
issn = {1533-4058},
mesh = {Biomarkers, Tumor/*genetics ; *Drug Delivery Systems ; Female ; Humans ; Receptors, Neuropeptide/*genetics/metabolism ; Receptors, Pituitary Hormone-Regulating Hormone/*genetics/metabolism ; Triple Negative Breast Neoplasms/*diagnosis/*genetics ; },
abstract = {PURPOSE: Growth hormone-releasing hormone (GHRH) has been shown to modify the growth behavior of many cancers, including breast. GHRH is produced by tumor cells, acts in an autocrine/paracrine manner, and requires the presence of GHRH receptor (GHRH-R) on the tumor cells to exert its effects. GHRH activity can be effectively blocked by synthetic antagonists of its receptor and hence, the expression of GHRH-R by tumor cells could serve as a predictor of response to GHRH-R antagonist therapy. In this study, we investigated the expression of GHRH-R in triple-negative breast cancers (TNBC). As TNBCs are morphologically and immunophenotypically heterogenous, the staining results were also correlated with the histologic subtypes of these tumors.

MATERIALS AND METHODS: On the basis of histomorphology and immunophenotype, 134 cases of primary TNBCs were further subdivided into medullary, metaplastic, apocrine, and invasive ductal carcinomas of no special type (IDC-NST). Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were assessed semiquantitatively as negative, low expression, moderate, and high expression.

RESULTS: Of the 134 TNBCs, 85 were classified as IDC-NST, 25 as metaplastic, 16 as medullary, and 8 as apocrine carcinoma. Overall, positive reaction for GHRH-R was seen in 77 (57%) of tumors including 66 (77.6%) of IDC-NST. All medullary carcinomas were negative for GHRH-R and, with the exception of 1 case with low expression, none of the metaplastic carcinomas expressed GHRH-R (P<0.005).

CONCLUSIONS: A considerable number of TNBCs are positive for GHRH-R as a predictor of potential response to anti-GHRH-R treatment. This expression however, varies considerably between histologic subtypes of triple-negative breast cancers. Although most medullary and metaplastic carcinomas do not express GHRH-R, three fourths of the IDC-NST show a positive reaction. Testing for GHRH-R expression is therefore advisable if anti-GHRH-R therapy is being considered.},
}

Biomarkers, Tumor/*genetics
*Drug Delivery Systems
Female
Humans
Receptors, Neuropeptide/*genetics/metabolism
Receptors, Pituitary Hormone-Regulating Hormone/*genetics/metabolism
Triple Negative Breast Neoplasms/*diagnosis/*genetics

@article {pmid29215790,
year = {2018},
author = {Carrascal, MA and Silva, M and Ramalho, JS and Pen, C and Martins, M and Pascoal, C and Amaral, C and Serrano, I and Oliveira, MJ and Sackstein, R and Videira, PA},
title = {Inhibition of fucosylation in human invasive ductal carcinoma reduces E-selectin ligand expression, cell proliferation, and ERK1/2 and p38 MAPK activation.},
journal = {Molecular oncology},
volume = {12},
number = {5},
pages = {579-593},
pmid = {29215790},
issn = {1878-0261},
support = {P01 HL107146/HL/NHLBI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Breast Neoplasms/*enzymology/pathology ; Carcinoma, Ductal, Breast/*enzymology/pathology ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; E-Selectin/genetics/*metabolism ; Female ; Fucose/analogs & derivatives/pharmacology ; Fucosyltransferases/*antagonists & inhibitors ; Humans ; Ligands ; MAP Kinase Signaling System/drug effects ; Middle Aged ; Neoplasm Invasiveness ; Oligosaccharides/*metabolism ; Primary Cell Culture ; Sialyl Lewis X Antigen ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; },
abstract = {Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLe[X][/A]), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their role in breast carcinogenesis is still unknown. Here, we aimed to define the contribution of the fucosylated structures, including sLe[X][/A] , to cell adhesion, cell signaling, and cell proliferation in invasive ductal carcinomas (IDC), the most frequent type of breast cancer. We first analyzed expression of E-selectin ligands in IDC tissue and established primary cell cultures from the tissue. We observed strong reactivity with E-selectin and anti-sLe[X][/A] antibodies in both IDC tissue and cell lines, and expression of α-1,3/4 FUTs FUT4, FUT5, FUT6, FUT10, and FUT11. To further assess the role of fucosylation in IDC biology, we immortalized a primary IDC cell line with human telomerase reverse transcriptase to create the 'CF1_T cell line'. Treatment with 2-fluorofucose (2-FF), a fucosylation inhibitor, completely abrogated its sLe[X][/A] expression and dramatically reduced adherence of CF1_T cells to E-selectin under hemodynamic flow conditions. In addition, 2-FF-treated CF1_T cells showed a reduced migratory ability, as well as decreased cell proliferation rate. Notably, 2-FF treatment lowered the growth factor expression of CF1_T cells, prominently for FGF2, vascular endothelial growth factor, and transforming growth factor beta, and negatively affected activation of signal-regulating protein kinases 1 and 2 and p38 mitogen-activated protein kinase signaling pathways. These data indicate that fucosylation licenses several malignant features of IDC, such as cell adhesion, migration, proliferation, and growth factor expression, contributing to tumor progression.},
}

Adult
Aged
Breast Neoplasms/*enzymology/pathology
Carcinoma, Ductal, Breast/*enzymology/pathology
Cell Adhesion/drug effects
Cell Line, Tumor
Cell Proliferation/drug effects
E-Selectin/genetics/*metabolism
Female
Fucose/analogs & derivatives/pharmacology
Fucosyltransferases/*antagonists & inhibitors
Humans
Ligands
MAP Kinase Signaling System/drug effects
Middle Aged
Neoplasm Invasiveness
Oligosaccharides/*metabolism
Primary Cell Culture
Sialyl Lewis X Antigen
p38 Mitogen-Activated Protein Kinases/genetics/*metabolism

@article {pmid29217299,
year = {2018},
author = {Zahorchak, AF and Macedo, C and Hamm, DE and Butterfield, LH and Metes, DM and Thomson, AW},
title = {High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.},
journal = {Cellular immunology},
volume = {323},
number = {},
pages = {9-18},
pmid = {29217299},
issn = {1090-2163},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; R34 AI123033/AI/NIAID NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; },
mesh = {B7-2 Antigen/*immunology ; B7-H1 Antigen/*immunology ; Cell Differentiation/immunology ; Dendritic Cells/cytology/*immunology ; Humans ; Interleukin-10/immunology ; Lymphocyte Activation ; Monocytes/immunology ; Organ Transplantation/methods ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Regulatory/immunology ; Transplantation Immunology ; },
abstract = {Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naïve and memory allogeneic CD4[+] and CD8[+] T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8[+] T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway.},
}

B7-2 Antigen/*immunology
B7-H1 Antigen/*immunology
Cell Differentiation/immunology
Dendritic Cells/cytology/*immunology
Humans
Interleukin-10/immunology
Lymphocyte Activation
Monocytes/immunology
Organ Transplantation/methods
T-Lymphocyte Subsets/immunology
T-Lymphocytes, Regulatory/immunology
Transplantation Immunology

@article {pmid29227474,
year = {2018},
author = {Lehmann, LH and Jebessa, ZH and Kreusser, MM and Horsch, A and He, T and Kronlage, M and Dewenter, M and Sramek, V and Oehl, U and Krebs-Haupenthal, J and von der Lieth, AH and Schmidt, A and Sun, Q and Ritterhoff, J and Finke, D and Völkers, M and Jungmann, A and Sauer, SW and Thiel, C and Nickel, A and Kohlhaas, M and Schäfer, M and Sticht, C and Maack, C and Gretz, N and Wagner, M and El-Armouche, A and Maier, LS and Londoño, JEC and Meder, B and Freichel, M and Gröne, HJ and Most, P and Müller, OJ and Herzig, S and Furlong, EEM and Katus, HA and Backs, J},
title = {A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.},
journal = {Nature medicine},
volume = {24},
number = {1},
pages = {62-72},
pmid = {29227474},
issn = {1546-170X},
mesh = {Animals ; Epigenesis, Genetic ; Gene Transfer Techniques ; Heart Failure/genetics/*metabolism ; Hexosamines/*biosynthesis ; Histone Deacetylases/genetics/*metabolism ; Mice ; Mice, Knockout ; *Myocardial Contraction ; Myocardium/enzymology ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/metabolism ; Physical Conditioning, Animal ; Proteolysis ; Stromal Interaction Molecule 1/metabolism ; },
abstract = {The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.},
}

Animals
Epigenesis, Genetic
Gene Transfer Techniques
Heart Failure/genetics/*metabolism
Hexosamines/*biosynthesis
Histone Deacetylases/genetics/*metabolism
Mice
Mice, Knockout
*Myocardial Contraction
Myocardium/enzymology
Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/metabolism
Physical Conditioning, Animal
Proteolysis
Stromal Interaction Molecule 1/metabolism

@article {pmid29246496,
year = {2018},
author = {Hannafon, BN and Ding, WQ},
title = {miRNAs as Biomarkers for Predicting the Progression of Ductal Carcinoma in Situ.},
journal = {The American journal of pathology},
volume = {188},
number = {3},
pages = {542-549},
pmid = {29246496},
issn = {1525-2191},
support = {U54 GM104938/GM/NIGMS NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/genetics/metabolism ; Breast Neoplasms/genetics/metabolism/*pathology ; Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology ; Disease Progression ; Female ; Humans ; MicroRNAs/genetics/*metabolism ; },
abstract = {Ductal carcinoma in situ (DCIS) is defined as a proliferation of neoplastic cells within the duct of the mammary gland that have not invaded into the surrounding stroma. DCIS is considered a precursor to invasive ductal carcinoma (IDC); however, approximately half of DCIS may progress to IDC, if left untreated. Current research has shown that the genomic and transcriptomic changes are present in DCIS before the emergence of invasive disease, indicating that the malignant nature of the DCIS is defined before invasion. However, important questions remain surrounding the specific changes and processes required for malignant progression and identification of prognostic indicators of aggressiveness. miRNAs are small regulatory RNAs that can modulate gene expression by complementary binding to target mRNAs and inducing translational repression and/or mRNA degradation. In the past decade, research has shown that miRNA expression is dysregulated in IDC and that these changes are already present at the DCIS stage. Therefore, changes in miRNA expression may provide the necessary information to identify a clinical indicator of the aggressiveness of DCIS. Herein, we review the miRNA signatures identified in DCIS, describe how these signatures may be used to predict the aggressiveness of DCIS, and discuss future perspectives for DCIS biomarker discovery.},
}

Biomarkers, Tumor/genetics/metabolism
Breast Neoplasms/genetics/metabolism/*pathology
Carcinoma, Intraductal, Noninfiltrating/genetics/metabolism/*pathology
Disease Progression
Female
Humans
MicroRNAs/genetics/*metabolism

@article {pmid29275106,
year = {2018},
author = {Inoue, Y and Yamashita, N and Kitao, H and Tanaka, K and Saeki, H and Oki, E and Oda, Y and Tokunaga, E and Maehara, Y},
title = {Clinical Significance of the Wild Type p53-Induced Phosphatase 1 Expression in Invasive Breast Cancer.},
journal = {Clinical breast cancer},
volume = {18},
number = {4},
pages = {e643-e650},
doi = {10.1016/j.clbc.2017.11.008},
pmid = {29275106},
issn = {1938-0666},
mesh = {Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/genetics/*pathology/surgery ; Carcinoma, Ductal, Breast/genetics/*pathology/surgery ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Comparative Genomic Hybridization ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Copy Number Variations ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Neoplasm Staging ; Prognosis ; Protein Phosphatase 2C/genetics/*metabolism ; Tumor Suppressor Protein p53/genetics ; },
abstract = {BACKGROUND: Wild type p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved.

MATERIALS AND METHODS: Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available. We evaluated Wip1 and p21 protein expression (201 cases), Wip1 mRNA expression (63 cases), PPM1D DNA copy number (71 cases) and TP53 status (36 cases) using available samples among the 201 cases, and analyzed their relationships with clinicopathological factors and prognosis.

RESULTS: The nuclear expression of Wip1 protein was positive in 21 cases (10.4%). The PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. The tumors with positive Wip1 and negative p21 expression showed the poorest prognosis among all tumor types.

CONCLUSION: The protein expression of Wip1 might be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression was associated with the poorest prognosis and suggests the loss of p53 function.},
}

Adult
Aged
Aged, 80 and over
Breast Neoplasms/genetics/*pathology/surgery
Carcinoma, Ductal, Breast/genetics/*pathology/surgery
Cell Line, Tumor
Cell Nucleus/metabolism
Comparative Genomic Hybridization
Cyclin-Dependent Kinase Inhibitor p21/metabolism
DNA Copy Number Variations
Female
Humans
Immunohistochemistry
Middle Aged
Mutation
Neoplasm Staging
Prognosis
Protein Phosphatase 2C/genetics/*metabolism
Tumor Suppressor Protein p53/genetics