PURPOSE: Several studies indicate that nonsteroidal anti-inflammatory drugs including aspirin and sulindac reduce the risk of colon cancer. Futhermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) are shown to inhibit the development colon cancer in animal models of carcinogenesis. COX-1 is constitutively expressed to fulfill its beneficial housekeeping roles. COX-2 is not constitutively expressed by most normal tissues, but it is rapidly induced by certain inflammatory cytokines, tumor promoters, growth factors and oncogenes. The purpose of this study is to evaluate the role of COX-2 in colorectal carcinoma development and the correlation between COX-2 expression and tumor angiogenesis and p53 overexpression. METHODS: Immunohistochemical analyses using antibodies against COX-2, factor VIII-related antigen, vascular endothelial growth factor (VEGF) and p53 were carried out on archival specimens of 15 colorectal adenoma and 41 adenocarcinoma. RESULTS: COX-2 expression was increased in 5/15 (33.3%) adenomas and 24/41 (58.5%) adenocarcinomas. COX-2 expression in adenocarcinoma was nearly significantly higher than in adenoma (P=0.050). In adenocarcinoma, COX-2 expression was increased in early cancer (TNM stage) (P=0.028) and well differentiated tumor (P=0.029). COX- 2 expression was not correlated with VEGF expression, microvessel density and p53 overexpression. CONCLUSIONS: These findings indicate that enhanced expression of COX-2 occurs early during colorectal cancer progression. However, further investigations are needed to evaluate the relationship of COX-2 and tumor angiogenesis using other laboratory methods.