| Backgrounds: Helicobacter pylori (H. pylori), infecting more than 50% of theworld population, has been found to be associated with various diseases including chronic gastritis, peptic ulcer diseases, and gastric neoplasms, usually located in the antral portion of the stomach. Epidemiological and animal studies demonstrated a link between gastric cancer (GC) or mucosal associated lymphoid tissue (MALT) lymphoma and chronic infection with Helicobacter pylori. Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduces the risk and spread of some cancers. NSAIDs inhibit cyclooxygenase (COX) activity. Cyclooxygenase, the key enzyme for synthesis of prostaglandins, exists in two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed in the gastrointestinal tract in large quantities and has been suggested to maintain mucosal integrity through continuous generation of prostaglandins. Cyclooxygenase-2 (COX-2), the inducible form of the rate-limiting enzyme for prostaglandin synthesis, is up-regulated in gastrointestinal cancers and is a keymediator of epithelial cell growth. The inducible COX-2 may play a role in gastric carcinogenesis. The exact mechanism responsible for the development of GC and MALT-lymphoma in H. pylori-infected patients still remains obscure. Since virulence of H. pylori in gastric carcinogenesis is reported to be associated with Cag A, we examined whether the presence of these virulence factors influenced the expression of COX-2 protein in gastric epithelial cells. AIMS: To investigate the relation between H pylori, CagA status and expression of COX-2 protein in gastric epithelial cells.Materials and Methods: Gastric biopsies from 120 subjects, 40 H. pylorinegative, 40 CagA~ H. pylori positive and 40 CagA* H. pylori positive, were examined immunohistochemically for COX-2 protein expressiono Anti-H. pylori IgG and anti-CagA IgG were estimated by ELISA tests. Patients were considered H. pylori positive if at least two of the four tests (histology. RUT. MC-UBT and serology) yielded positive results.Results : COX-2 protein expression localizes to the cytoplasmic region offoveolar and glandular epithelia. with variable levels in the epithelium. There was no correlation between COX-2 protein expression and the age or gender of patients. The positive rates of COX-2 protein expression in antral was significantly higher in H. pylori positive than in H. pylori negative (71.3 % vs 55%, p<0.05). There was a positive correlation between intensity of COX-2 protein expression and prevalence of H. pylori by Spearman correlation tests (rs=0.270, p<0.01). The colonization density of H. pylori (梸 +++)in the gastric antral mucosa was positive correlation with COX-2 expression (rs =0.323, PO.01) .The positive rates of COX-2 protein expression was significantly higher in CagA" H. pylori positive than in CagA"H. pylori (85 % vs 57.5%, p<0.05). There was a strongerly positive correlation between intensity of COX-2 protein expression and prevalence of CagA^H. pylori (rs =0.349, P<0.01) than prevalence ofH.pylori(r=0.270, p<0.01).The positive rates of COX-2 protein expression in antral was significantly higher in patients with dysplasia than intestinal metaplasia,chronic atrophic gastritis and chronic superficial gastritis (90% vs 80%,50%,43.3%,respectively, p<0.01). COX-2 protein expression was significantly higher in patients with gastric precancerous conditions than non-precancerous conditions (85 % vs 46.7%, p<0.001). The positive rates of COX-2 protein expression was a positive correlation with gastric histopathology (rs =0.409, PO.001) .Conclusion:1) H. pylori infection leads to gastric mucosal overexpression of COX-2 protein and there is a positive correlation between colonization intensity of H. pylori and COX-2 protein expression, suggesting that the enzyme is involved in H. pvlori-related gastric pathogenesis in humans.2) There is a strongerly positive correlation between intensity of COX-2 protein expression and prevalence of Cag...
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