Relationship of Helicobacterpylori CagA Status to Gastric Cell Proliferation and Apoptosis

Despite the fact that the association ofHelicobacter pylori with an increased risk of gastriccancer is well documented, the exact mechanisms of thisassociation have not been elucidated. Our aim was to shed some light on these mechanisms by studyingthe relationship of H. pylori CagA status to gastriccell proliferation and apoptosis, since both play animportant role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fiftypatients [32 men, 18 women, median age 39.5 years (range18-67)], referred for upper gastrointestinal endoscopy,from whom antral biopsies were taken. On biopsy specimens gastritis was estimated byscoring the severity of inflammatory infiltrate, and thepresence of atrophy and intestinal metaplasia were alsonoted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelialapoptotic index (AI) was measured by special stainingfor apoptosis, and CagA status was determinedserologically by immunoblotting the sera of patientsagainst H. pylori antigens. Thirty-eight (76%) of the50 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 thedifference in PI between the H. pylori CagA(+) and H. pylori (-) groups was highly significant (P< 0.001). Concerning apoptosis, in the H. pyloriCagA(+) 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 theH. pylori CagA(-) and H. pylori (-) groups, wassignificant (P < 0.05). We conclude that H. pyloriCagA(+) strains induce increased gastric cellproliferation, which is not accompanied by a parallel increasein apoptosis. This might explain the increased risk forgastric carcinoma that is associated with infection byH. pylori CagA(+) strains.