Expression of cyclooxygenase‐2 protein in colon disease

OBJECTIVE: Several epidemiological studies have indicated that the long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of colorectal cancer. The best known action of NSAIDs is to block cyclooxygenase, the key enzyme required for the conversion of arachidonic acid to prostaglandins. Two cyclooxygenase isoforms have been identified and these are referred to as COX-1 and COX-2. Recent studies indicate that inducible COX-2 plays an important role in gastrointestinal inflammation and carcinogenesis. The present study was undertaken to investigate the expression and clinical implications of COX-2 and COX-1 in normal and diseased colons. METHODS: COX-2 and COX-1 protein expression in specimens from normal controls and diseased colon tissues were examined semiquantitatively by using immunohistochemical methods. RESULTS: By using immunohistochemical detection methods, low COX-2 protein expression in colonic epithelial cells was observed in 20.0% (2/10) of normal controls. Eighty percent (16/20) of specimens from inflammatory bowel disease (IBD) had a high COX-2 expression, 46.40% (13/28) of adenomas and 64.3% of (9/14) well-differentiated colonic carcinomas had some COX-2 protein expression. Expression of COX-2 protein was increased in IBD and colonic carcinomas compared with normal controls. There were no significant differences between colonic adenomas and colonic carcinomas. No correlation was found between COX-2 protein expression and patient gender, patient age, tumor size, tumor location or the degree of differentiation/ metastasis of the tumor. Strong immunoreactive COX-2 was expressed in clusters in interstitial cells (mainly mononuclear cells) in 53.6% (15/28) of adenomas and 64.3% (9/14) of colonic carcinomas. Strong COX-2 protein expression was also displayed in the normal glands that were adjacent to the adenomas and carcinomas. Expression of COX-1 protein was observed in the epithelial cells and interstitial cells or tumor cells of normal colon, IBD, colonic adenomas and colonic carcinomas. CONCLUSIONS: Our results indicated that COX-2 protein overexpression may contribute to the development of IBD and colonic carcinogenesis.