Promoter methylation of p16, DAPK, CDH1, and TIMP-3 genes in cervical cancer: correlation with clinicopathologic characteristics

Int J Gynecol Cancer. May-Jun 2006;16(3):1234-40. doi: 10.1111/j.1525-1438.2006.00522.x.


This study was conducted to investigate the promoter methylation status of the p16, DAPK, CDH1, and TIMP-3 genes in primary cervical cancer and its correlation with clinicopathologic characteristics. Promoter methylation was evaluated using a methylation-specific polymerase chain reaction in 78 cervical cancer tissue specimens and 24 control, normal cervical tissue specimens. Clinicopathologic parameters were obtained from medical records, and the relationship between the discrete variables and the methylation status was evaluated. The frequencies of promoter methylation of p16, DAPK, CDH1, and TIMP-3 in cervical cancer were 57%, 44.9%, 52.6%, and 9%, respectively. Primary cervical cancer had significantly higher methylation frequencies for the p16 and DAPK promoters than did the control, normal cervix (P < 0.0001). The promoter methylation of TIMP-3 was significantly higher in adenocarcinoma than in squamous cell carcinoma (41.7% vs 3%, respectively, P= 0.0175). High-stage cancers exhibited an increased promoter methylation frequency for p16 (P= 0.0061). The promoter methylation of the p16 gene is a frequent event in cervical carcinogenesis and may have potential clinical application as a marker for the progression and prognosis of cancer.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Apoptosis Regulatory Proteins / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cervix Uteri / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Methylation*
  • DNA, Neoplasm / metabolism
  • Death-Associated Protein Kinases
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Promoter Regions, Genetic*
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology


  • Apoptosis Regulatory Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • Tissue Inhibitor of Metalloproteinase-3
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases