Expression of cyclooxygenase-2 in human sporadic colorectal adenomas

Background: Aspirin and other NSAIDs are effective chemopreventive agents in colorectal neoplasia but the mechanisms by which they work remain unclear although inhibition of cyclooxygenase-2 (COX-2) is thought to be a key molecular target. COX-2 is overexpressed in the majority of human colorectal cancers (CRC) and in a variable proportion of colonic adenomas. However, there are conflicting data regarding the extent and localisation of COX-2 expression within adenomatous polyps. Aim: To assess COX-2 expression in colonic polyps of varying sizes and immediately adjacent normal mucosa. Methods: Immunohistochemistry for COX-2 was performed on 35 normal mucosal biopsies and 49 colonic polyps from 35 patients. Expression and localisation of COX-2 was studied using an antihuman COX-2 isoform specific antibody. Immunoreactivity was detected by signal amplification following heat induced antigen retrieval. A CRC tissue microarray was used as a positive control. Results: The colorectal cancer cores exhibited positive staining in the cytoplasm of neoplastic epithelial cells. All (100%) of the normal mucosal sections were negative for COX-2 staining. In contrast, 69% of the polyps stained positive for COX-2 (p<0.001). Of these, 77% displayed immunoreactivity within the stroma alone and 23% showed positivity in the neoplastic epithelium, with or without stromal positivity. Immunoreactivity was focal with stromal positivity mainly localised to the periphery of the polyp lesions. 80% of large polyps (>1 cm) and 55% of small polyps (⩽1 cm) were positive for COX-2 (large v small p<0.001). Conclusion: COX-2 expression was demonstrated in the majority of colonic adenomas. Localisation of this was mainly in stromal cells. The stromal microenvironment of colonic adenomas and its interface with neoplastic epithelium may be important in cellular transformation towards malignancy, and warrants further investigation