In India, breast cancer is the second most common malignant condition among women. It is hereditary in 10% of cases, the majority related to mutations in the BRCA1 and BRCA2 genes. The presence of BRCA germline mutations in breast/ovarian carcinomas has been shown to have prognostic and therapeutic significance. Identification of tumours with BRCA defects has therapeutic and prognostic implications. Our objective was to assess whether immunohistochemical analysis (IHC) for BRCA is an effective method for the detection of BRCA dysfunction in hereditary breast carcinoma or not.
We have selected 231 patients for BRCA1/2 mutation detection during Aug.2010 to Oct.2015 from the breast cancer patients attended our hospital, NCRI. After taking written consent 4-5ml peripheral blood and/or operated tissue (where possible) were collected from BC patients. BRCA1/2 mutations were identified by ARMS-PCR, DNA sequencing and whole genome sequencing. We performed IHC staining with BRCA1 and BRCA2 antibody to distinguish tumour status between patients according to their indication of BRCA1 or BRCA2 mutation.
Average age of the patients was 45.87±1.57 yrs. BRCA1/2 mutations were identified in 24 (10.38%) patientsthrough above mentioned methods. Tumour samples fromnine BRCA positive cases and 15BRCA negative cases were chosen for investigation of IHC. Out of 9 samples with BRCA mutations, 7were BRCA immunostainingnegative, with absence of nuclear or cytoplasmic staining. On the otherhand, from the 15 patients negative for mutations in both genes, 12 were positive for BRCA1immunostaining with a clear nuclear immunoreactivity in tumour cells. From ROCcurve analysis, it was found that IHC negativity (area- 0.211, CI: 0.011-0.411) isassociated (p = 0.02) with BRCA positivity.
In conclusion, we observed a high specificity for the prediction of BRCA1/2 carriers withimmunohistochemistry using BRCA antibody. Validation of this assay, using a larger sample, will allow using immunohistochemistry to decide which high-risk patients should be screenedfirst for the BRCA mutation gene.
Clinical trial identification
Legal entity responsible for the study
Netaji Suibhas Chandra Bose Cancer Research Institue
All authors have declared no conflicts of interest.