Clinicopathological implications of inactivation of RASSF1A in serous epithelial ovarian cancers

To investigate the frequency of promoter hypermethylation of RASSF1A gene in ovarian cancers and its correlations to gene expression and clinicopathological characters in the Chinese population.

In this study, we detected the frequency of promoter hypermethylation of the RASSF1A gene in 60 patients with primary serous epithelial ovarian carcinomas (SEOCs) using Methylation-Specific PCR (MSP). The gene expression of mRNA and protein was examined by RT-PCR and Western blot.

The frequency of promoter hypermethylation of RASSF1A in Chinese primary SEOCs was 53.3%, whereas promoter hypermethylation was not found in normal ovarian tissues and benign ovarian tissues. The expression of both mRNA and protein of RASSF1A was significantly down-regulated or lost in the methylated group than in nonmethylated group (p < 0.05, respectively). SEOCs with Stage III, IV exhibited a higher frequency of RASSF1A promoter hypermethylation (70.4%, 81.8%) than those with Stage I or Stage II (16.7%, 20.0%, p < 0.05, respectively). Hypermethylation patterns in RASSF1A were more frequently detected in poorly differentiated SEOCs (78.6%) than in moderately differentiated (23.8%) or in well-differetiated SEOCs (27.3%, p < 0.05, respectively).

The high frequency of promoter hypermethylation of RASSF1A contributes to the gene expression in Chinese primary SEOCs. The inactivation of the RASSF1A gene due to hypermethylation in the promoter region might play a critical role in the pathogenesis of ovarian cancers.