Association of BRCA 1 and BRCA 2 Protein Expression in Breast Cancers With Their Histological Phenotype by Immunohistochemistry in Indigenous Black Malawians Presenting at Queen Elizabeth Central Hospital

Abstract

Breast Cancer gene 1 (BRCA1) and Breast Cancer gene 2 (BRCA2) have gained major scientific interest as potential prognostic and predictive markers for various tumours. Management of breast cancer depends on availability of robust clinical and pathological prognostic and predictive factors to guide patient decision making and the choice of treatment options. One of the prognostic factors of breast cancer is the BRCA1 and BRCA2 protein expression. Immunohistochemical studies on formalin-fixed, paraffin-embedded (FFPE) tumours have demonstrated a loss or reduction of protein expression, not only in BRCA1 associated breast carcinomas, but also in non-BRCA1 associated familial and sporadic breast carcinomas. Immunohistochemical information might guide therapy selection for patients. To study association of the expression of BRCA1 and BRCA2 protein with their histological phenotype by immunohistochemistry in Malawian females presenting with breast cancer at Queen Elizabeth Central Hospital (QECH). Materials and Methods:This was a laboratory based cross sectional study in which 63 Formalin-Fixed,Paraffin-Embeded(FFPE) breast cancer tissue samples from QECH and College of Medicine in Malawi were analysed. Tissues were cut for histological analysis and immunohistochemical staining using a microtome. Haematoxylin and eosin staining was done on slides to confirm invasive breast cancer, then underwent immunohistochemical staining with BRCA1 MS110 monoclonal antibodies and BRCA2 polyclonal antibodies. Data analysis was done using SPSS version 20.0 for windows. The statistical test used was Pearson chi square and fishers exact test where necessary. Sixty three FFPE breast cancer tissues were analysed from the year 2012 to 2015. The histological phenotypes that were found in the study were; invasive ductal carcinoma (IDC) 41.3% (26/63), invasive lobular carcinoma (ILC) 27% (17/63), medullary carcinoma 6.4% (4/63) and others 25.4% (16/63). The age of the patients in our study ranged from 21 to 82 years. The most affected age group was between 31 to 60 years. However, the peak age group was between 41 to 50 years. The different histological phenotypes showed a varied expression of both BRCA1 and BRCA 2 protein. Medullary carcinoma had the highest expression with 100% retention of both BRCA1 and BRCA 2. The study showed the peak age for breast cancer presentation to be between 41-50years. Invasive ductal carcinoma was the predominant histological phenotype representing 41.3% of all the breast cancer samples. The overall retention for BRCA1 was 49.2% and 46% BRCA2. This shows that more than half of the breast cancer presenting at QECH had lost both the BRCA1 and BRCA 2 expression and suggests an aggressive course of these malignancies.