TIMP-2 gene methylation in cervical precursor and invasive lesions

Exp Mol Pathol. 2015 Feb;98(1):119-23. doi: 10.1016/j.yexmp.2015.01.008. Epub 2015 Jan 9.

Abstract

Objective: To analyze the presence of HPV-DNA and TIMP-2 gene methylation in cervical precursor and invasive lesions, as well as to study the associations among the latter, the presence of HPV-DNA, and the clinical evolution of such lesions.

Methods: Cross-sectional study that includes 49 biopsy or brush smear samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal cervices were analyzed.

Results: TIMP-2 gene methylation was detected in 86.8% (33/38) of the samples from the group with lesions and 50% (4/8) of the normal samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was more frequent in the methylated samples (50%), and the group with methylation had a higher risk of unfavorable evolution than the group without methylation; however, such observations were not statistically significant (p=0.19).

Conclusion: TIMP-2 gene methylation and the presence of HPV-DNA were characteristic of the group with cervical lesions. Methylation was not associated with the presence of HPV-DNA or an unfavorable clinical evolution.

Keywords: Cervix; Methylation; Neoplasia; Papillomavirus infection; TIMP-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cross-Sectional Studies
  • DNA Methylation*
  • DNA, Viral / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Papillomaviridae / genetics
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Polymerase Chain Reaction
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*
  • Uterine Cervical Dysplasia / genetics*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • DNA, Viral
  • Tissue Inhibitor of Metalloproteinase-2