Clinical significance of BRCA1 and BRCA2 mRNA and protein expression in patients with sporadic gastric cancer

Abstract

The purpose of the present study was to investigate the clinical significance of BRCA1/BRCA2 DNA repair associated (BRCA1/BRCA2) gene expression in patients with sporadic gastric cancer (GC) who had received postoperative adjuvant chemotherapy. Breast cancer type 1 and 2 susceptibility protein (BRCA1 and BRCA2) expression and BRCA1/BRCA2 mRNA expression were evaluated using immunohistochemistry (IHC) and in-situ hybridization (ISH) on tissue GC microarray tissues, in addition to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results were analyzed for clinicopathological associations. A total of 367 cases of sporadic GC (stages II and III) were subjected to BRCA1 and BRCA2 expression analysis, and for BRCA1 and BRCA2 IHC, 360 cases were informative. A total of 61 cases (16.9%) displayed a loss of BRCA1 and 63 (17.5%) displayed a loss of BRCA2. BRCA1 and BRCA2 ISH results were obtained in 364 cases, of which 98 (26.9%) presented with low expression of BRCA1 mRNA and 148 (40.7%) with low expression of BRCA2 mRNA. In 72 of the 367 cases, BRCA1 and BRCA2 mRNA expression levels were assessed using RT-qPCR, of which 50 (69.4%) and 56 (77.8%) displayed low expression of BRCA1 and BRCA2, respectively. Positive IHC expression of BRCA2 was associated with advanced tumor stage; however, BRCA1 expression was not associated with any clinicopathological parameters. Associations between the RT-qPCR and ISH methods were not significant for either BRCA1 or BRCA2. The results of Kaplan-Meier survival analysis with stage subgrouping revealed no significant differences with regard to survival rate. Of the multivariate analyses, neither BRCA1 nor BRCA2 IHC results were independent prognostic factors. In summary, the present study indicated that BRCA1 and BRCA2, as assessed by IHC, may be used as clinicopathological biomarkers to evaluate the prognosis of sporadic GC.