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

Abstract

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.

• Authors: K Saukkonen, O Nieminen, B van Rees, S Vilkki, M Härkönen, M Juhola, J P Mecklin, P Sipponen, A Ristimäki
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 7 Issue 7 Pg. 1923-31 (Jul 2001) ISSN: 1078-0432 [Print] United States
• PMID: 11448905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Membrane Proteins
• RNA, Messenger
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Adenocarcinoma (enzymology, pathology)
• Adult
• Aged
• Cyclooxygenase 2
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Intestines (pathology)
• Isoenzymes (genetics, metabolism)
• Male
• Membrane Proteins
• Middle Aged
• Prostaglandin-Endoperoxide Synthases (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Stomach (enzymology, pathology)
• Stomach Neoplasms (enzymology, pathology)
• Tumor Cells, Cultured