BRCA immunohistochemistry for screening of BRCA mutation in epithelial ovarian cancer patients

Gynecol Oncol Rep. 2020 May 27;33:100582. doi: 10.1016/j.gore.2020.100582. eCollection 2020 Aug.

Abstract

To evaluate BRCA1/2 immunohistochemistry (IHC) as a screening test for germline BRCA1/2 in epithelial ovarian cancer (EOC), tumor tissue from 105 EOC patients who had germline BRCA mutations, including 9 BRCA1 mutations, 6 BRCA2 mutations and 90 no BRCA mutations, were studied. Paraffin-embedded tissue blocks were stained for BRCA1 and BRCA2. Tumors were indicated as a loss of BRCA expression when neoplastic nuclear stained less than 10%. Loss of BRCA1 and/or BRCA2 expression was found in 36 patients (34.3%). BRCA1 IHC loss was found in 21 patients (20%) while 24 patients (22.9%) had BRCA2 IHC loss. There were no significant differences in patient characteristics between both groups. Loss of BRCA1 expression had 66.7% sensitivity, 84.3% specificity, 28.6% positive predictive value (PPV), and 96.4% negative predictive value (NPV) for detection of germline BRCA1 mutation. Meanwhile, loss of BRCA2 expression had 50% sensitivity, 78.8% specificity, 12.5% PPV, and 96.3% NPV for detection of germline BRCA2 mutation. There was no significant difference in survival outcomes between both groups. Based on high NPV, BRCA IHC may be useful to exclude patients without BRCA dysfunction if IHC showed intact expression. Only patients with BRCA IHC loss should be offered further genetic testing.

Keywords: BRCA mutation; Immunohistochemistry; Ovarian cancer.