Enhanced expression of activation-induced cytidine deaminase in human gastric mucosa infected by Helicobacter pylori and its decrease following eradication

摘要

Background: Recent studies have shown important roles for activation-induced cytidine deaminase (AID), an intrinsic genome mutator, in H. pylori-associated gastric cancer development. Here, we evaluated the relationship between H. pylori-induced gastritis and AID expression from human biopsy specimens. Methods: In 109 patients with dyspeptic symptoms who had undergone endoscopy and received biopsy of the antrum, angulus, and corpus, H. pylori infection was diagnosed by serologic test, 13C urea breath test, and histological examination. Histological scores of H. pylori, neutrophils, mononuclear cells, atrophy, and intestinal metaplasia (IM) were assessed using the updated Sydney system (USS). Immunohistochemical AID expression of the biopsy specimens was scored. Results: Sixty of 109 (55.0 %) patients were positive for H. pylori and eradication was successful in 48 patients. AID expression in H. pylori-infected mucosa was significantly higher (p 0.01) than in non-infected mucosa. AID expression was highest in the antrum and was significantly (p 0.01) reduced toward the proximal portion of the stomach. For USS, multivariate analysis using linear regression revealed that mononuclear cell infiltration (p 0.01) and IM (p 0.05) correlated independently with AID expression. After eradication of H. pylori, AID expression was significantly decreased (p 0.01), but was still higher than that in H. pylori-negative patients in all sites of the stomach. Conclusions: AID expression is elevated in H. pylori-positive patients and is reduced following H. pylori eradication. Moreover, AID expression is highest in the antrum and correlated with severity of chronic inflammation and IM, suggesting an important role for AID in gastric cancer development through gastritis.