Relationship of Helicobacter pylori CagA status to gastric cell proliferation and apoptosis

Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer is well documented, the exact mechanisms of this association have not been elucidated. Our aim was to shed some light on these mechanisms by studying the relationship of H. pylori CagA status to gastric cell proliferation and apoptosis, since both play an important role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fifty patients [32 men, 18 women, median age 39.5 years (range 18-67)], referred for upper gastrointestinal endoscopy, from whom antral biopsies were taken. On biopsy specimens gastritis was estimated by scoring the severity of inflammatory infiltrate, and the presence of atrophy and intestinal metaplasia were also noted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelial apoptotic index (AI) was measured by special staining for apoptosis, and CagA status was determined serologically by immunoblotting the sera of patients against H. pylori antigens. Thirty-eight (76%) of the 50 patients were H. pylori (positive) and 12 (24%) H. pylori (negative). Among the 38 H. pylori(+) patients, 28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups, the PI values [median (ranges)] were 5 (4-7) and 3.7 (3.5-5.5), respectively (P < 0.05). In addition the difference in PI between the H. pylori CagA(+) and H. pylori(-) groups was highly significant (P < 0.001). Concerning apoptosis, in the H. pylori CagA(+) and CagA(-) groups, the values for AI were 1 (1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between the H. pylori CagA(-) and H. pylori(-) groups, was significant (P < 0.05). We conclude that H. pylori CagA(+) strains induce increased gastric cell proliferation, which is not accompanied by a parallel increase in apoptosis. This might explain the increased risk for gastric carcinoma that is associated with infection by H. pylori CagA(+) strains.