Cyclooxygenase‐2 expression during carcinogenesis in the human stomach

Abstract

The prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with a reduced risk of gastric cancer. The best-known target of these drugs is cyclooxygenase (COX); the COX-2 isoform is frequently up-regulated in gastric adenocarcinomas. Using the post-gastrectomy stomach as a model, the expression of COX-2 mRNA and protein has been investigated during tumour progression in the human stomach. COX-2 expression was comparable in gastric stump carcinomas and conventional gastric carcinomas and localized primarily to the cytoplasm of the neoplastic cells. COX-2 mRNA was elevated in biopsies containing intestinal metaplasia, as determined by reverse transcriptase polymerase chain reaction (RT-PCR). COX-2 immunopositivity became more frequent during progression from reactive epithelium to high-grade dysplasia, both in the epithelial and in the stromal cell compartment. Co-localization of COX-2-positive stromal cells was seen with CD68, alpha-smooth muscle actin (alpha-SMA), vimentin, and HLA-DR, but an as yet unidentified subpopulation of stromal cells remained. Co-localization with the macrophage marker CD68 was only observed in a minority of COX-2-positive cells. These data show that COX-2 expression is a relatively early event during carcinogenesis in the stomach. COX-2 expression increases during tumour progression in the stomach, suggesting a role for COX-2 expression in gastric tumourigenesis.

Cyclooxygenase‐2 expression in human pituitary tumors

“…There is convincing evidence that NSAIDs, which are inhibitors of cyclooxygenase activity, lower the risk of developing carcinoma of the colon, 6,35,36 esophagus, 9,11,37 and stomach. 10,38 Although the potential therapeutic efficacy of NSAIDs was related exclusively to tumors located in the digestive tract, some studies have suggested that COX-2 may be the target for the prevention and treatment of other carcinomas, including those of the prostate, 8,39 breast, 13,40,41 pancreas, 12,42 head and neck, 43 and the urinary bladder. 44,45 To our knowledge, no epidemiologic studies have been performed to determine the protective effects of COX-2 inhibitors on the development and progression of pituitary tumors.…”

Cyclooxygenase-2 Expression

“…In fact, our findings were obtained by analysis of a relatively large number of consecutively resected cases in a single institution and, thus, should be of considerable interest. Moreover, the monoclonal antibodies we used have been shown in several excellent studies (13,14,30,31,38) and is considered to give the most sensitive, specific, and reproducible immunoreactivity of Cox-2 protein. Nevertheless, as proposed by Buecher et al (28), it will be of critical importance to standardize the methods used for the evaluation of tumor Cox-2 status and to apply common interpretative criteria to allow direct comparison of results between laboratories.…”

Expression of COX-2 proteins in gastric mucosal lesions

“…COX-2 overexpression was found in most of gastric body adenocarcinoma and some cardia adenocarcinoma tissues. It is necessary to further confirm the status of COX-2 expression in gastric cancer tissues, especially the characteristics of COX-2 overexpression related to typing, degree, differentiation and lymph node metastasis [11][12][13][14][15] . We studied the COX-2 expression at gene and protein levels in tissues with gastric mucosal lesion, and explored the relationship between COX-2 expression and gastric carcinoma and H pylori infection at pathological and pathophysiological levels.…”