The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia

Cyclooxygenase 2 (COX-2) overexpression has been described in sporadic colo nic neoplasia, but its role in ulcerative colitis (UC) neoplastic progressi on remains unexplored. Although the specific role of cyclooxygenase in colo nic neoplasia is uncertain, its inhibition by nonsteroidal anti-inflammator y drugs decreases the risk of sporadic colonic adenocarcinoma and causes re gression of adenomas in familial adenomatous polyposis. To investigate the role of COX-2 in UC-associated neoplasia, we assessed COX-2 protein and mRN A expression throughout the spectrum of UC-associated neoplastic lesions in four total colectomy specimens, using immunocytochemistry and a novel TaqM an reverse transcriptase-polymerase chain reaction assay. The findings were correlated with DNA ploidy and inflammatory activity. We found COX-2 overe xpression throughout the neoplastic spectrum in UC (P < 0.0001, R-2 = 0.53) , even in diploid samples that were negative for dysplasia. Overall, neopla stic change explained 53% of the variation in COX-2 expression, whereas inf lammatory activity explained only 11%. COX-2 was overexpressed in all aneup loid samples and in 38% of diploid samples (P = 0.0074). cDNA representatio nal difference analysis was also performed and revealed that COX-2 mRNA was an up-regulated cDNA representational difference analysis difference produ ct. COX-2 overexpression occurs early in UC-associated neoplasia, and the i ncrease cannot be explained by inflammatory activity alone. The data sugges t that COX-2-specific inhibitors may have a chemopreventative role in UC bu t the possibility that they could exacerbate UC inflammatory activity needs to be tested.