Expression of Cyclooxygenase-2 in Dysplasia of the Stomach and in Intestinal-type Gastric Adenocarcinoma

• Published in: Clinical cancer research 2001-07, Vol.7 (7), p.1923-1931
• Main Authors: SAUKKONEN, Kirsi, NIEMINEN, Outi, VAN REES, Bastiaan, VILKKI, Susa, HÄRKÖNEN, Matti, JUHOLA, Matti, MECKLIN, Jukka-Pekka, SIPPONEN, Pentti, RISTIMÄKI, Ari
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - enzymology; Adenocarcinoma - pathology; Adult; Aged; Biological and medical sciences; Cyclooxygenase 2; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intestines - pathology; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Medical sciences; Membrane Proteins; Middle Aged; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stomach - enzymology; Stomach - pathology; Stomach Neoplasms - enzymology; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Cells, Cultured; Tumors
• ISSN: 1078-0432; 1557-3265

Purpose: Cyclooxygenase (Cox) is the key enzyme in conversion of arachidonic acid to prostanoids. Two Cox genes have been cloned, and expression of Cox-2 mRNA and protein has been shown to be elevated in several human malignancies and in animal models of carcinogenesis. The purpose of this study was to investigate Cox-2 protein expression in human gastric dysplasias and adenocarcinomas. Experimental Design: Performance of several Cox-2 antibodies was evaluated, after which Cox-2 protein expression was studied in 67 gastric cancer specimens and in eight definitive dysplasias by using immunohistochemistry. Results: Cox-2 positivity was detected in 58% (25/43) of the intestinal-type (well-differentiated) tumors and 6% (1/18) of diffuse-type (poorly differentiated) tumors. Consistent with these data, we detected higher expression of Cox-2 mRNA, protein, and enzymatic activity in well-differentiated gastric cancer cell lines (MKN-28 and MKN-74) when compared with poorly differentiated cell lines (HSC-39 and KATO III). Cox-2 immunoreactivity was localized to the carcinoma cells, but the stroma of the tumors was negative. However, strong Cox-2 positivity was consistently detected in stromal cells at sites of erosions and ulcerations. Furthermore, four of nine (44%) definitive dysplasias of the stomach that showed no evidence of invasion were positive for Cox-2. Conclusions: Cox-2 is expressed by the neoplastic cells in the intestinal-type gastric adenocarcinoma and by precarcinogenic (dysplastic) lesions leading to this disease.