COX-2 overexpression as a biomarker of early cervical carcinogenesis: a pilot study

Gynecol Oncol. 2007 Oct;107(1 Suppl 1):S155-62. doi: 10.1016/j.ygyno.2007.07.023. Epub 2007 Sep 10.

Abstract

Background: Recent studies have demonstrated that cyclooxygenase-2 (COX-2) expression is up-regulated in a number of cancers. Selective inhibition of COX-2 offers a potential pharmacological strategy for cancer prevention. The COX-2 isoform is induced in response to inflammatory factors and is expressed in premalignant lesions, including cervical tissues. Few studies have investigated COX-2 expression as a biomarker for early cervical carcinogenesis. In this preliminary study, we assessed the variability of COX-2 overexpression in cervical premalignant lesions.

Methods: Fifty-two patients were recruited and consented. Paired abnormal and control (normal) cervical biopsies were obtained and evaluated for high-risk human papillomavirus (HPV), inflammation, histopathological diagnosis, and COX-2 protein concentration by ELISA. Paired Student's t-test and general linear regression models were used to compare mean COX-2 protein concentrations among biopsy samples and selected risk variables.

Results: Forty-seven of fifty-two paired biopsies were evaluated. COX-2 protein concentrations were 4.9-fold greater in abnormal biopsies (CIN 1 and CIN 2) than normal biopsies. COX-2 was also significantly increased in inflammation-positive biopsies. No significant association was found between COX-2 levels and HPV high-risk positivity, age, parity, STI history, or hormonal contraceptive use, but the sample size was small.

Conclusions: These results suggest that COX-2 induction begins in the premalignant phase of cervical carcinogenesis and is correlated with inflammation. A trial using a much larger number of specimens will allow further development of our understanding of COX-2 as a biomarker for use in chemoprevention trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Case-Control Studies
  • Cyclooxygenase 2 / biosynthesis*
  • Female
  • HeLa Cells
  • Humans
  • Inflammation / enzymology
  • Inflammation / pathology
  • Inflammation / virology
  • Linear Models
  • Middle Aged
  • Papillomavirus Infections / enzymology
  • Papillomavirus Infections / pathology
  • Pilot Projects
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • Cyclooxygenase 2