Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis.

PURPOSE

To investigate the role of epigenetic inactivation of hMLH1 during the malignant transformation of ovarian endometriosis (EMs), and to explore the relationship between the epigenetic inactivation of hMLH1 in eutopic endometria and the malignant transformation of ovarian EMs.

METHODS

The target tissue from 29 cases of the endometriosis-associated ovarian carcinoma (EAOC) group, 20 cases of EMs group and 16 cases of control endometrium (CEs) group was obtained by laser capture microdissection (LCM). The methylation statue of hMLH1 promoter was determined by methylation-specific PCR (MSP) and the protein expression of hMLH1 was analysed by immunohistochemistry.

RESULTS

The frequency of promoter hypermethylation of hMLH1 in the neoplastic tissue or ectopic endometria of the EAOC group was higher than that of the EMs group (p < 0.05), and the frequency of promoter hypermethylation of hMLH1 in eutopic endometria of the EAOC group was higher than that of the EMs and CEs groups (p < 0.05). In addition, the protein expression of hMLH1 in eutopic endometria of the EAOC group was lower than that of the EMs and CEs group (p < 0.05), and absence of hMLH1 protein expression was significantly correlated with promoter hypermethylation of the gene.

CONCLUSIONS

Epigenetic inactivation of hMLH1 was an early event in the malignant transformation of ovarian EMs. Epigenetic inactivation of hMLH1 in eutopic endometria was synchronous with that in ectopic endometria and the epigenetic inactivation of hMLH1 in eutopic endometria of EMs might be a potential molecular tool for early diagnosis of the malignant transformation of ovarian EMs.