West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 18 12 2017 12 01 BRCA1 Promoter Methylation and Expression - Associations with ER+, PR+ and HER2+ Subtypes of Breast Carcinoma 3293 3299 53198 10.22034/APJCP.2017.18.12.3293 EN Mohit Kumar Department of Pathology, University Of Delhi, Delhi, India. Ram Krishna Sahu Division of Molecular Oncology, National Institute of Cancer Prevention and Research (ICMR), I-7 Sector 39, Noida, Utter Pradesh, India. Aditi Goyal Department of Pathology, University Of Delhi, Delhi, India. Sonal Sharma Department of Pathology, University Of Delhi, Delhi, India. Navneet Kaur Department of Surgery UCMS and GTB Hospital, University Of Delhi, Delhi, India. Ravi Mehrotra Division of Molecular Cytology, National Institute of Cancer Prevention and Research (ICMR), I-7 Sector 39, Noida, Utter Pradesh, India. 0000-0001-9453-1408 Usha Rani Singh Department of Pathology, University Of Delhi, Delhi, India. Suresh Hedau Division of Molecular Oncology, National Institute of Cancer Prevention and Research (ICMR), I-7 Sector 39, Noida, Utter Pradesh, India. 0000-0002-9576-1341 Journal Article 2017 07 07 Introduction: Considering the increasing trend in incidence rates, morbidity and mortality of breast cancer, there is an urgent need to identify and validate new biomarkers for early detection and better management. The purpose of the study was to investigate BRCA1 protein expression and promoter methylation of the BRCA1 gene and their association with molecular subtypes based on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) positivity. Materials and Methods: A total of 114 breast cancer tissue biopsies were collected for methylation specific PCR (MSP) and immunohistochemical (IHC) analysis. Results: Seven tissue microarrays were constructed. BRCA1 protein expression was reduced in 55/114 (48.2%) and in the majority of ER-negative tumors (73.3%) (p<0.001). Similarly BRCA1 expression was reduced in the majority of PR-negative tumors (69.2%) but without statistical significance (p value=0.083). BRCA1 methylation was positive in 59.6% cases. A subset regarding ER+, PR+ and HER2+ was identified which consisted of 31.6% in which an inverse relationship between BRCA1 methylation and protein expression was noted. Conclusion: Reduced expression was associated with ER and PR negative status which is linked with a poor prognosis. BRCA1 protein expression might thus be used as a prognostic indicator to predict treatment response to hormone therapy.

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