The hypermethylation and protein expression of p16^INK4A and DNA repair gene O⁶ -methylguanine-DNA methyltransferase in various uterine cervical lesions

Purpose: This study is aimed at investigating the significance of gene promoter methylation status and protein expression of p16^INK4A and O⁶-methylguanine-DNA methyltransferase (MGMT) in the various uterine cervical lesions. Materials and methods: Methylation status by using methylation-specific polymerase chain reaction (MS-PCR) and protein expression by using immunohistochemistry for p16^INK4A and MGMT genes were performed in cervical squamous intraepithelial neoplasms (CIN), invasive squamous cell carcinomas (SCC), adenocarcinomas and non-neoplastic cervices. Results: None of 20 non-neoplastic cervices showed p16^INK4A and MGMT gene hypermethylation, whereas at least one of these genes was hypermethylated with 50.0% (5/10) of CIN I, 65.0% (13/20) of CIN II-III, 70.2% (33/47) of SCC and 85.0% (17/20) of adenocarcinoma. p16^INK4A protein was totally negative in non-neoplastic cervices, but positive with 90.0% of CIN I, 100% of CIN II-III and adenocarcinoma, and 78.7% of SCC. MGMT protein was expressed in 10% of non-neoplastic cervices, but significantly increased in SCC (42.5%) and adenocarcinoma (70.0%). The protein expression of p16^INK4A and MGMT was not related to their gene promoter methylation status. Conclusions: The hypermethylation of p16^INK4A and MGMT genes in the uterine cervix may indicate the presence of malignant cells, and p16^INK4A immunostaining is useful in grading CIN and diagnosing invasive SCC and adenocarcinoma.