HELICOBACTER-PYLORI CAGA(-CELL PROLIFERATION FROM APOPTOSIS() STRAINSAND DISSOCIATION OF GASTRIC EPITHELIAL)

Background: Infection with Helicobacter pylori induces chronic gastrit is in virtually all infected persons, and such gastritis has been asso ciated with an increased risk of developing gastric cancer, This risk is further enhanced with cagA(+) (positive for cytotoxin-associated ge ne A) H. pylori strains and may be a consequence of induced gastric ce ll proliferation and/or alteration in apoptosis (programmed cell death ) in the gastric epithelium. Purpose: To determine whether the H. pylo ri cagA genotype and another virulence-related characteristic, the vac A (vacuolating cytotoxin A) sla genotype, differentially affect epithe lial cell proliferation, apoptosis, and the histologic parameters of i nflammation and injury, we quantitated these characteristics in infect ed and uninfected persons. Methods: Fifty patients underwent upper gas trointestinal endoscopy, and biopsy specimens were taken, Apoptotic ce lls in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine tr iphosphate; epithelial cell proliferation was scored by immunohistoche mical analysis of the proliferation-associated antigen Ki-67, Antibodi es directed against H. pylori and CagA protein were measured in the se rum of patients by means of enzyme-linked immunosorbent assays. Analys is of H., pylori genomic DNA, by use of the polymerase chain reaction, was performed to determine the cagA and vacA genotypes. Acute and chr onic inflammation, epithelial cell degeneration, mucin depletion, inte stinal metaplasia, glandular atrophy, and vacuolation were each scored in a blinded manner. Reported P values are two-sided. Results: Person s harboring cagA(+) strains (n = 20) had significantly higher gastric epithelial proliferation scores than persons infected with cagA(-) str ains (n = 9) or uninfected persons (n = 21) (P = .025 and P < .001, re spectively), but the difference in cell proliferation between the latt er two groups was not statistically significant, The number of apoptot ic cells per 100 epithelial cells (apoptotic index) in persons infecte d with cagA(+) strains was lower than in persons infected with cagA(-) strains (P = .05). Apoptotic indices in the cagA(+) group were simila r to those in the uninfected group (P = .2), Epithelial cell prolifera tion was significantly correlated with acute gastric inflammation, but only in the cagA(+) group (r = .44; P = .006), The cagA(+) and vacA s la genotypes were found to be concordant, confirming the close relatio nship between these virulence-related genotypes. Conclusions: Gastric mucosal proliferation was significantly correlated with the severity o f acute gastritis in persons infected with cagA(+) vacA sla strains of H. pylori. This increased proliferation was not accompanied by a para llel increase in apoptosis, Implications: Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain t he heightened risk for gastric carcinoma that is associated with infec tion by cagA(+) vacA sla strains of H. pylori.