BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co-expression of DNA methyltransferases

Abstract

The breast cancer susceptibility gene 1 (<i>BRCA1</i>) inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation of <i>BRCA1</i> methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation of <i>BRCA1</i> in benign and malignant ovarian tumor tissues, to establish the association with the clinicopathological significance and the prognostic value. Additionally, the contribution of DNA methyltransferase (DNMT) expression to <i>BRCA1</i> promoter hypermethylation was determined. The rate of <i>BRCA1</i> methylation was observed to be 35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the benign tumors. <i>BRCA1</i> methylation was significantly associated with the downregulation of <i>BRCA1</i> expression (P<0.001) and the frequency of <i>BRCA1</i> methylation was greater in the carcinomas of patients whose tumor was bilateral than that of patients with a unilateral carcinoma (P=0.015). <i>BRCA1</i> methylation was significantly associated with the preoperative serum carbohydrate antigen-125 level (P=0.013), improved overall survival (P=0.005) and disease-free survival (P=0.007). In addition, a significant correlation was observed between the co-expression of DNMTs and the methylation status of <i>BRCA1</i>. Thus, the present study provided support for <i>BRCA1</i> promoter hypermethylation as a prognostic marker for survival in sporadic EOC, and co-expression of DNMTs was observed to contribute to <i>BRCA1</i> promoter hypermethylation.