Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix

Pathol Int. 2015 Sep;65(9):476-85. doi: 10.1111/pin.12332. Epub 2015 Jul 27.

Abstract

Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors.

Keywords: adenocarcinoma; methylation; prognosis; squamous cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Alphapapillomavirus / classification*
  • Alphapapillomavirus / genetics
  • Alphapapillomavirus / isolation & purification
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / genetics
  • Cervix Uteri / pathology
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Methylation
  • Disease-Free Survival
  • Female
  • Human Papillomavirus DNA Tests
  • Humans
  • Immunoglobulins / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / pathology
  • Prognosis
  • Tumor Suppressor Proteins / genetics
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CADM1 protein, human
  • CDKN2A protein, human
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Cyclin-Dependent Kinase Inhibitor p16
  • Immunoglobulins
  • Neoplasm Proteins
  • RASSF1 protein, human
  • SPZ1 protein, human
  • Tumor Suppressor Proteins