Lorena Alves Teixeira

BRCA1 Expression by Immunohistochemistry and Prognosis in Ovarian Cancer: A Systematic Review and Meta-Analysis

Homologous recombination deficiencies are associated with increased platinum sensitivity and potential response to poly (ADP-ribose) polymerase inhibitors in epithelial ovarian cancer. As an alternative to germline testing or somatic tumor sequencing, BRCA1 deficiency can be detected by immunohistochemistry and might predict homologous recombination deficiencies. This study aimed to assess the association between BRCA1 expression by immunohistochemistry and the prognosis of patients with epithelial ovarian cancer. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We searched PubMed, EMBASE, Web of Science, and Scopus databases through July 2019. Reference lists of selected articles were screened for further studies. We conducted qualitative synthesis and meta-analyses of hazard ratios for overall survival and progression-free survival. Of 41 studies of BRCA1 expression using immunohistochemistry, 18 evaluated the association of BRCA1 expression with patient survival (2738 cases). The loss of BRCA1 expression was associated with improved overall survival (hazard ratio = 0.67, 95% confidence interval 0.57-0.77) and progression-free survival (hazard ratio = 0.70, 95% confidence interval 0.58-0.84). Negative BRCA1 expression assessed by immunohistochemistry was associated with a better prognosis in epithelial ovarian cancer.

Immunohistochemistry for the detection of BRCA1 and BRCA2 proteins in patients with ovarian cancer: a systematic review

Background Loss of function in either breast cancer type 1 susceptibility protein (BRCA1) or breast cancer type 2 susceptibility protein (BRCA2) is a major risk factor for epithelial ovarian cancer (EOC) development. BRCA1 or BRCA2 deficiencies are associated with short-term prognosis and might have importance for the treatment of women with the disease. However, the screening of all possible mechanisms of dysfunction is expensive, time-consuming and difficult to apply in clinical practice. On the other hand, immunohistochemistry (IHC) is a simple and reliable method to access the expression of several proteins in tumour tissues. Materials and methods This systematic review aims to evaluate the current usage of IHC to detect BRCA1 and BRCA2 deficiencies in EOC. We searched and evaluated all primary literature on the use of IHC for evaluating BRCA1 and BRCA2 proteins expression in EOC. The main concepts for the search were: ovarian neoplasms, IHC, BRCA1 and BRCA2. Results Forty-four studies from 925 unique titles were included. A total of 4206 tumour samples were evaluated for BRCA1 and 1041 for BRCA2 expression. Twelve BRCA1 primary antibodies were used in 41 studies, and the most common was the MS110 clone (75.6%). Seven BRCA2 primary antibodies were used in ten studies. Using the cut-off of 10%, 47.0% of EOCs are associated with loss of BRCA1 and 34.5% with the loss of BRCA2 expression. Conclusion IHC was effective to detect loss of BRCA1 protein expression in EOC; however, data on BRCA2 expression were heterogeneous and difficult to interpret.