Premalignant cervical lesions are characterized by dihydrofolate reductase gene amplification and c-Myc overexpression: possible biomarkers

J Low Genit Tract Dis. 2007 Oct;11(4):265-72. doi: 10.1097/LGT.0b013e31803c4df0.

Abstract

Objective: The c-Myc oncoprotein deregulation is associated with overall genomic instability and locus-specific genomic instability involving the dihydrofolate reductase (DHFR) locus. This study analyzes c-Myc protein levels and the stability of the DHFR gene in cervical tissue biopsies.

Materials and methods: The stability of the DHFR gene was examined by fluorescence in situ hybridization (FISH). c-Myc protein levels were evaluated using quantitative fluorescent immunohistochemistry. Forty-four cervical tissue biopsies were analyzed and included 33 preinvasive cervical lesions identified by histology, 14 samples were cervical intraepithelial neoplasia (CIN) 1; 7 were CIN 2; and 12 were CIN 3. Eleven biopsies had negative histology.

Results and conclusion: c-Myc protein levels were elevated in CIN 1, 2, and 3 (p = .02) biopsies. Concomitantly, DHFR gene amplification was detected in CIN 1, 2, and 3 (p = .0001). The degrees of DHFR gene amplification and of c-Myc protein levels were a measure of the progressive degree of the lesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Colposcopy
  • Cytogenetic Analysis
  • Female
  • Frozen Sections
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Tetrahydrofolate Dehydrogenase / genetics*
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Tetrahydrofolate Dehydrogenase