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Increased Expression of Cyclooxygenase-2 Protein in Human Gastric Carcinoma

Departments of Hematology and Oncology [H. Y. L., J. H. C., J. W. Y., M. S. Y., D. Y. C., H. S. K., D. K. N., H. C. K.] and Pathology [H. J. J., K. B. L.], Ajou University School of Medicine, Suwon 442-721, Korea

Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein overexpression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.

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