Inactivation of O6-methyguanine-DNA methyltransferase by promoter hypermethylation: Association of epithelial ovarian carcinogenesis in specific histological types

Aim: The aim of this study was to evaluate O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation, MGMT expression and microsatellite instability (MSI), as well as to elucidate their correlation with clinical and pathological parameters in epithelial ovarian cancer. Methods: Ovarian cancer tissue specimens (n = 86) were obtained after a staging operation. The MGMT gene was investigated by methylation-specific polymerase chain reaction (MSP) and MGMT expression status was analyzed using immunohistochemistry. MSI status was examined by the fluorescence-based PCR using five National Cancer Institute markers. Results: Negative MGMT expression was detected in 12 of 86 (14.0%) epithelial ovarian cancers. In 34 cases where MSP results were available, MGMT promoter hypermethylation was detected in five cases (14.7%) with mucinous or clear cell carcinomas, but not in any of other histological types (P = 0.031). Five out of six cases with negative MGMT expression showed MGMT promoter hypermethylation, whereas all of the 28 cases that retained expression of MGMT were unmethylated at the MGMT CpG island (P