Enhanced cyclooxygenase-2 expression in sporadic and familial adenomatous polyposis of the human colon

Background: The cyclooxygenase (COX) enzymes exist in two related but uniqu e isoforms (COX-1 and COX-2) and catalyze the formation of prostaglandins ( PGs). COX-1 is constitutively expressed, and is responsible for the synthes is of PGs necessary for gastroprotection and normal renal function. The COX -2 isoform is important in a variety of pathophysiological conditions such as inflammation and tumorigenesis. Numerous studies report that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) can decrease the inciden ce of some tumor types, including gastrointestinal polyposis. Methods: In t his study, we evaluated COX-1 and COX-2 expression in 30 polyps collected f rom 10 patients with Familial adenomatous polyposis (FAP) and in 18 polyps collected from 18 patients with sporadic adenomatous polyposis (SAP) using COX-1 or COX-2 isoform-specific antibodies. All tissues were formalin-fixed and paraffin-embedded, Immunoreactivity was detected using tyramide signal amplification and evaluated utilizing an immunohistochemical scoring syste m. Results: COX-2 was minimally detected in the distant non-neoplastic epit helium, which also served as an internal negative control. In comparison, a ll polyps collected from SAP or FAP patients overexpressed COX-2 in the neo plastic epithelial cells (P less than or equal to 0.002). Additionally, pro nounced COX-2 expression was observed in the stromal cells underlying and a djacent to adenomatous lesions. COX-1 immunoreactivity was weak to mild thr oughout each tissue evaluated and did not change in the neoplastic or strom al cells of the polyps. Conclusions: COX-2 expression is upregulated in the adenomatous epithelium of SAP and FAP, while the COX-1 isoform appears to be constitutively expressed at low levels in both neoplastic and nonneoplas tic regions. The differential expression of COX-1 and COX-2 in these neopla sms suggests that COX-2 rather than COX-1 may play a role in adenoma format ion and/or growth in cases of SAP and FAP in humans.