COX-2 overexpression as a biomarker of early cervical carcinogenesis: a pilot study.
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.
Saldivar
J Salvador
JS
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. bcrain@mdanderson.org
Lopez
David
D
Feldman
Rebecca A
RA
Tharappel-Jacob
Reena
R
de la Rosa
Antonio
A
Terreros
Daniel
D
Baldwin
William S
WS
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000821:virology; D016014:Linear Models; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000201:enzymology / Q000473:pathology; D010865:Pilot Projects; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000821:virology