Expression of cyclooxygenase-2 in dysplasia of the stomach and in intestinal-type gastric adenocarcinoma

Purpose: Cyclooxygenase (Cox) is the key enzyme in conversion of arachidoni c acid to prostanoids. Two Cox genes have been cloned, and expression of Co x-2 mRNA and protein has been shown to be elevated in several human maligna ncies and in animal models of carcinogenesis. The purpose of this study was to investigate Cox-2 protein expression in human gastric dysplasias and ad enocarcinomas. Experimental Design: Performance of several Cox-2 antibodies was evaluated, after which Cox-2 protein expression was studied in 67 gastric cancer spec imens and in eight definitive dysplasias by using immunohistochemistry. Results: Cox-2 positivity was detected in 58% (25/43) of the intestinal-typ e (well-differentiated) tumors and 6% (11 18) of diffuse-type (poorly diffe rentiated) tumors. Consistent with these data, we detected higher expressio n of Cox-2 mRNA, protein, and enzymatic activity in well-differentiated gas tric cancer cell lines (MKN-28 and MKN-74) when compared with poorly differ entiated cell lines (HSC-39 and KATO III). Cox-2 immunoreactivity was local ized to the carcinoma cells, but the stroma of the tumors was negative. How ever, strong Cox-2 positivity was consistently detected in stromal cells at sites of erosions and ulcerations. Furthermore, four of nine (44%) definit ive dysplasias of the stomach that showed no evidence of invasion were posi tive for Cox-2, Conclusions: Cox-2 is expressed by the neoplastic cells in the intestinal-t ype gastric adenocarcinoma and by precarcinogenic (dysplastic) lesions lead ing to this disease.