Cyclooxygenase-2 Expression and Colorectal Cancer
November 15, 1999
Cyclooxygenase-2 Expression and Colorectal Cancer
A pathogenic role for cyclooxygenase-2 has been suggested by the epidemiologic observational studies that demonstrate a reduced rate of colorectal adenomas and carcinomas in persons who have taken NSAIDs over long periods. Correspondingly, COX-2 has been found in human colorectal cancer, and interruption of COX-2 either by COX-2 specific inhibitors or COX-2 gene blockade substantially reduces polyp growth in mouse models of polyposis coli.
In order to further define the role of COX-2 in colorectal cancer, Sheehan and colleagues studied 76 patients with colorectal cancer, who had staining of the tumor epithelial cells with anti-COX-2 antibody. The degree of staining on a four-point scale (grade 1 = least staining, grade 4 = most staining) correlates with the degree of COX-2 expression. Survival, from the time of diagnosis to death, was compared in relation to COX-2 grade of staining.
All of the colorectal tumors stained positively for COX-2, dominantly in the cytoplasm of epithelial cells and/or vascular endothelial cells. In colon tissue samples from control samples without cancer, no COX-2 expression was demonstrable.
Numerous negative cancer outcome predictors were associated with COX-2 expression. For instance, there was a direct relationship between COX-2 staining and Dukes cancer stage, tumor size, and lymph node metastasis. Survival for 5 years was 40.5% in patients with grade 2-4 COX-2 staining, compared to 91.6% in patients with grade 1 COX-2 staining.
Sheehan et al acknowledge that it remains uncertain whether COX-2 plays a causal role in cancer and its progression, or is just an incidental association. Nonetheless, data with NSAIDs like sulindac have shown reductions in polyp number and size in high-risk populations, suggesting that COX activity may be not only pathogenic, but also modifiable.
Sheehan KM, et al. JAMA 1999;282: 1254-1257.
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