RESEARCH ARTICLE

BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays Abeer M. Mahmoud1,2,3*, Virgilia Macias2, Umaima Al-alem4, Ryan J. Deaton2, Andre Kadjaksy-Balla2, Peter H. Gann2, Garth H. Rauscher4

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1 College of Applied Health Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America, 2 Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America, 3 Department of Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt, 4 Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, United States of America * [email protected]

Abstract OPEN ACCESS Citation: Mahmoud AM, Macias V, Al-alem U, Deaton RJ, Kadjaksy-Balla A, Gann PH, et al. (2017) BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays. PLoS ONE 12(9): e0184385. https://doi.org/ 10.1371/journal.pone.0184385 Editor: Rajeev Samant, University of Alabama at Birmingham, UNITED STATES Received: July 2, 2017 Accepted: August 22, 2017 Published: September 1, 2017 Copyright: © 2017 Mahmoud et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: This work was supported by the National Institute of Health Grant # 2P50CA106743-06 to GHR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.

Purpose Mutations in BRCA1 are associated with familial as well as sporadic aggressive subtypes of breast cancer, but less is known about whether BRCA1 expression or subcellular localization contributes to progression in population-based settings.

Methods We examined BRCA1 expression and subcellular localization in invasive breast cancer tissues from an ethnically diverse sample of 286 patients and 36 normal breast tissue controls. Two different methods were used to label breast cancer tissues for BRCA1: (1) Dual immunofluoresent staining with BRCA1 and cytokeratin 8/18 and (2) immunohistochemical staining using the previously validated MS110 mouse monoclonal antibody. Slides were visualized and quantified using the VECTRA Automated Multispectral Image Analysis System and InForm software.

Results BRCA1 staining was more intense in normal than in invasive breast tissue for both cytoplasmic (p

BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays.

Mutations in BRCA1 are associated with familial as well as sporadic aggressive subtypes of breast cancer, but less is known about whether BRCA1 expres...
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