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

J Cancer Res Clin Oncol. 2005 Jun;131(6):364-70. doi: 10.1007/s00432-004-0657-5. Epub 2005 Mar 23.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cervical Intraepithelial Neoplasia / genetics
  • Cervical Intraepithelial Neoplasia / metabolism
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervix Uteri / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA / metabolism
  • DNA Methylation*
  • DNA Repair
  • Female
  • Gene Silencing
  • Humans
  • Immunoenzyme Techniques
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA
  • O(6)-Methylguanine-DNA Methyltransferase