Cyclooxygenase-2 expression in spontaneous intestinal neoplasia of domestic dogs

Cyclooxygenase-2 (Cox-2) is commonly upregulated during human colorectal tumorigenesis, and its contribution to this process has been clearly demonstrated in genetic mouse models. The only other species that naturally develops intestinal cancer with any frequency is the domestic dog. Intestinal carcinogenesis in humans has been strongly linked to environmental factors such as diet, which may be shared by household pets. We have previously reported that beta-catenin is overexpressed in the neoplastic epithelium of canine colorectal polyps, as it is in humans and rodents. We now show that Cox-2 is also upregulated in the majority of these lesions. Thirteen out of 20 colorectal adenomas (65%) contained immunohistochemically detectable Cox-2 protein restricted to the nonneoplastic tumor stroma, including myofibroblasts and a-smooth muscle actin-negative mesenchymal cells morphologically consistent with macrophages and/or fibroblasts. In contrast to benign polyps, seven of 15 adenocarcinomas (47%) also expressed Cox-2 in the neoplastic epithelium. These changes duplicate molecular changes in human intestinal tumorigenesis and substantiate a fundamental role for both beta-catenin and Cox-2 in intestinal neoplasia.