The hypermethylation and protein expression of p16INK4A 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 O-6-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.