Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis

Background-Helicobacter pylori, the main cause of chronic gastritis, is a c lass I gastric carcinogen. Chronic gastritis progresses to cancer through a trophy, metaplasia, and dysplasia. Precancerous phenotypic expression is ge nerally associated with acquired genomic instability. Aim-To evaluate the effect of H pylori infection and its eradication on gas tric histology, cell proliferation, DNA status, and oncogene expression. Methods/Subjects-Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patient s with H pylori negative chronic gastritis, 53 with H pylori positive chron ic gastritis, and 11 with gastric cancer. Results-All patients with chronic gastritis were in a hyperproliferative st ate related to mucosal inflammation, regardless of H pylori infection. Atro phy was present in three of 10 patients with H pylori negative chronic gast ritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patie nts with atrophy and H pylori infection; eight of these also had c-Myc expr ession, associated in six cases with p53 expression. Fifty three patients w ith H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastri tis activity; atrophy previously detected in 21/45 disappeared in five, reg ressed from moderate to mild in nine, and remained unchanged in seven; comp lete metaplasia disappeared in 4/14, and markers of genomic instability dis appeared where previously present. In the five patients in whom H pylori pe rsisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged. Conclusions-Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gast ritis; eradication of H pylori infection can reverse inflammation and the r elated atrophy, metaplasia, and genomic instability.