| Gastric cancer is a significant health problem in our locality. Its carcinogenesis remains incompletely understood. Recently, cyclooxygenase-2 (COX-2) expression has been found to be up-regulated in several human malignancies, including gastrointestinal cancer. The epidemiological observation of reduced cancer mortality associated with nonsteroidal anti-inflammatory drugs (NSAIDs) further suggests a role of COX-2 in carcinogenesis.; This study examined the expression of both COX-1 and COX-2 in normal gastric tissues, H. pylori-associated gastritis and benign gastric ulcers in order to enhance our understanding of COX expression in normal and benign gastric lesions. Our study thus focused on the expression of COX-2 in gastric carcinoma and on the possible relationships among COX-2 expression and genetic and epigenetic alterations of gastric cancer. Molecular alterations examined include microsatellite instability and promoter hypermethylation of DAP-kinase, E-cadherin, GSTP1, p14, p15, p16, and hMLH1.; This study has found that expression of COX-2 was up-regulated in gastric carcinoma, and such COX-2 over-expression may be associated with poor clinical outcome. Besides, an inverse relationship between COX-2 expression and the presence of high frequency microsatellite instability phenotype (MSI-H) was found, which is previously observed in colorectal cancer. This observation suggests that COX-2 expression and microsatellite instability represent two distinct pathways in gastric carcinogenesis.; This study also showed that in gastric cancer, concurrent hypermethylation of several gene promoters was a common epigenetic event, in which a link between hypermethylation of hMLH1 and MSI-H phenotype was observed. Moreover, the methylation status of hMLH1 was found to associate with COX-2 expression, whereas promoter hypermethylation of DAP-kinase was associated with poor prognosis in gastric carcinoma.; This study has demonstrated an up-regulation of COX-2 in both H. pylori-associated gastritis and gastric cancer, and it may further delineate possible relationships of COX-2 expression with other important genetic and epigenetic events in gastric carcinogenesis. |
