Localization of cyclooxygenase-2 in human sporadic colorectal adenomas

A putative target for the anti-colorectal cancer action of nonsteroidal ant i-inflammatory drugs is the inducible isoform of cyclooxygenase (COX), COX- 2. COX-2 is expressed within intestinal adenomas in murine polyposis models , but expression has been poorly characterized in human colorectal neoplasm s. Therefore, we investigated the localization of the COX-2 protein in huma n sporadic colorectal adenomas, Immunohistochemistry for COX-2 and CD68 (a tissue macrophage marker) was performed on formalin-fixed, paraffin-embedde d (n = 52) and frozen, acetone-fixed (n = 6) sections of human sporadic col orectal adenomas, Forty of 52 (77%) formalin-fixed adenomas expressed immun oreactive COX-2. COX-2 was localized to superficial interstitial macrophage s in 39 cases (75%) and to deep interstitial macrophages in 9 cases (17%). COX-2 staining of dysplastic epithelial cells was observed in 15 cases (29% ). A logistic regression analysis identified the adenoma site (P = 0.012) a nd histological type (P = 0.001) as independent predictors of superficial m acrophage COX-2 expression. There was no relationship between the number of macrophages within an adenoma and macrophage COX-2 expression. These resul ts indicate that COX-2 is expressed predominantly by interstitial macrophag es within human sporadic colorectal adenomas, If COX-2 does indeed play a r ole in the early stages of colorectal carcinogenesis in man, these data sug gest COX-2-mediated paracrine signaling between the macrophages and epithel ial cells within adenomas.