EXPRESSION OF BRCA1 AND BRCA2 BY IMMUNOHISTOCHEMICAL AND PROGNOSIS IN OVARIAN CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in the world. BRCA1 and BRCA2 proteins, frequently altered in EOC, are a potential predictive biomarkers for risk assessment, prognostic, and therapeutic response to platinum-based chemotherapy and PARP inhibitors. Despite numerous independent studies using the immunohistochemical (IHC) to assess these proteins expression and the relationship with survival in EOC patients, the results remain controversial. Aim This study aimed to synthesize the scientific evidence regarding the use of IHC for detecting BRCA1 and BRCA2 proteins in EOC and relationship with the prognosis. Method This study followed the PRISMA guidelines. Studies analyzing the BRCA1 and BRCA2 IHC expression in EOC patients were identified through systematic searches in PubMed, Embase, Web of Science, Scopus databases through June 2019. Meta-analyzes of fixed and random effects models were performed with a hazard ratio (HR) and 95% confidence intervals (95%CI) for overall survival (OS) and progression-free survival (PFS). The quality of each study was evaluated by the Newcastle-Ottawa Scale (NOS) and the European Lung Cancer Working Party (ELCWP). Results Of the 44 studies eligible for the systematic review (4,735 patients), 50% of the tumors presented low BRCA1 expression (41 studies) and 61% of BRCA2 (ten studies). Fourteen studies have linked the expression of BRCA1 with survival and were included for this meta-analysis. However, there was no possibility of combining the results of BRCA2 expression. Reduced BRCA1 expression was associated with better OS (HR = 0.77, 95%CI = 0.60-0.99) and PFS (HR = 0.75, 95%CI = 0.59-0.94). The heterogeneity between the survival studies disappeared after the categorization according to the MS110 antibody, 10% cut-off point and high quality by the NOS and ELCWP scales (I2 = 34%,p = 0.15). Subgroup analysis using the MS110 antibody and 10% cut-off showed a statistical difference between negative versus positive expression of BRCA1 in favor of low expression for OS (HR = 0.67, 95%CI = 0.55-0.82) and PFS (HR = 0.81, 95%CI = 0.70-0.94). Conclusions Negative BRCA1 expression in EOC patients appeared to have a better prognosis. However, there is no universal standard protocol with translational applicability for the identification of alterations in BRCA1 and BRCA2 proteins by IHC. Larger and prospective studies are required to validate these findings. PROSPERO protocol registration CRD42017070405.

Publication History

Article published online:
23 October 2019