Cyclooxygenase-2 (Cox-2) Expression during Carcinogenesis in Ulcerative Colitis-Associated Neoplasia
B Santoni, M Berho. Cleveland Clinic Florida, Weston
Background: Cox-2 is commonly expressed in sporadic colorectal cancer, but little is known regarding its role in ulcerative colitis (UC) - related carcinogenesis. The aim of this study was to investigate the presence of Cox-2 over-expression in the UC-associated dysplasia-carcinoma lesions and surrounding inflamed tissue.
Design: Institutional Review Board approval was obtained for this study, A total of 190 patients were divided into 5 groups as follows: (1) UC-associated colorectal carcinoma (n=48), (2) UC and dysplasia (n=62), (3) long standing (>10 years) UC without carcinoma or dysplasia (n=34), (4) sporadic colorectal cancer (n=30), (5) non-UC and non-colorectal cancer (constipation, diverticulosis) (n=16). All patients had multiple tissue specimens evaluated for Cox-2 expression sampled from five locations: normal colorectal mucosa (INF-), inflamed mucosa (INF+), high-grade dysplasia (HGD), low-grade dysplasia (LGD), and carcinoma. Cox-2 over-expression was detected by immunohistochemistry in paraffin-embedded sections using a monoclonal Cox-2 antibody. Degree of staining was graded semi-quantitatively using criteria previously described. Generalized Estimating Equations (GEEs) were used to model predictors of Cox-2 expression.
Results: COX-2 expression varied by tissue location (p<0.0001), and disease (p=0.018). Over expression of cox-2 was significantly higher in UC-related carcinoma than in inflamed and non inflamed mucosa (p<0.0001), but not significantly different from areas of HGD or LGD. There was also evidence suggesting that HGD and LGD are significantly higher than inflamed and non inflamed mucosa. Over expression of Cox-2 was significantly higher in inflamed mucosa than in non-inflamed mucosa (p=0.008). Tissue location is a stronger predictor of Cox-2 expression than is disease. Duration of Ulcerative colitis is a statistically significant predictor of Cox-2 expression.
Conclusions: These results suggest that Cox-2 overexpression may be involved in the progression from inflamed mucosa to dysplasia to carcinoma in UC This finding may impact on the therapeutic management of UC, as COX-2 inhibitors could reduce and/or slow the risk of cancer development in these patients.
Monday, March 22, 2010 11:00 AM
Platform Session: Section E, Monday Morning