Role of Cyclooxygenase-2 on development and progression of colorectal cancer and its chemopreventive effect.

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Although accumulated knowledge has shown that cyclooxygenase-2(COX-2) plays an important role in the occurrence and the progression of colorectal tumor, the mechanism how COX-2 promotes colorectal tumorigenesis remains unclear. One intriguing finding is that the expression of COX-2 impairs the apoptotic response. In this study we investigated when COX-2 protein starts to overexpress in colorectal tumors in the process of developing cancer from adenoma and whether COX-2 expression correlates with proliferation and/or apoptosis in human sporadic colorectal cancers. MATERIALS & METHODS : A retrospective review of patients with early colorectal tumor was performed. Immunohistochemical analysis was performed on paraffin-embedded tissue samples using a COX-2 antibody. Proliferation and apoptosis were investigated on serial sections by Ki-67 antibody and TUNEL method as well as p53 immunohistochemistry. COX-2 score, Ki-67 labeling index, apoptotic index and p53-positive ratio were calculated … More at both surface and deeper parts of the tumor. The relationship between Ki-67 labeling index or apoptotic index, p53-positive ratio and COX-2 score at each part of the tumor was analyzed. RESULTS : In colorectal tumors, marked expression of immunoreactive COX-2 was present not only in interstitial cells including inflammatory mononuclear cells, vascular endothelial cells and fibroblasts, but also in tumor cells. In proportion as the tumor increased in size, COX-2 positive ratio increased. The COX-2 score and p53 positive ratio at deeper part of cancers were higher than those at surface part. Ki-67 labeling index at deeper part was significantly lower than that at surface part. At surface part the COX-2 score of p53-positive cancers was higher than that of p53-negative cancers. The apoptotic index showed no correlation with COX-2 score. At deeper part, on the other hand, lower apoptotic index correlated with higher COX-2 score. The Ki-67 labeling index and p53 positive ratio showed no correlation with COX-2 score. The apoptotic index of p53-positive cancers was significantly lower than that of p53-negative cancers at both surface and deeper parts. CONCLUSIONS : These evidences support the hypothesis that COX-2 promotes development of colorectal tumors, one of which mechanisms is to prevent apoptosis with p53-independent pathway. Less