BACKGROUND: Infection with Helicobacter pylori induces chronic gastritis in 
virtually all infected persons, and such gastritis has been associated with an 
increased risk of developing gastric cancer. This risk is further enhanced with 
cagA+ (positive for cytotoxin-associated gene A) H. pylori strains and may be a 
consequence of induced gastric cell proliferation and/or alteration in apoptosis 
(programmed cell death) in the gastric epithelium.
PURPOSE: To determine whether the H. pylori cagA genotype and another 
virulence-related characteristic, the vacA (vacuolating cytotoxin A) s1a 
genotype, differentially affect epithelial cell proliferation, apoptosis, and 
the histologic parameters of inflammation and injury, we quantitated these 
characteristics in infected and uninfected persons.
METHODS: Fifty patients underwent upper gastrointestinal endoscopy, and biopsy 
specimens were taken. Apoptotic cells in the specimens were quantitated after 
terminal deoxynucleotidyl transferase labeling of DNA fragments with 
digoxigenin-deoxyuridine triphosphate; epithelial cell proliferation was scored 
by immunohistochemical analysis of the proliferation-associated antigen Ki-67. 
Antibodies directed against H. pylori and CagA protein were measured in the 
serum of patients by means of enzyme-linked immunosorbent assays. Analysis of H. 
pylori genomic DNA, by use of the polymerase chain reaction, was performed to 
determine the cagA and vacA genotypes. Acute and chronic inflammation, 
epithelial cell degeneration, mucin depletion, intestinal metaplasia, glandular 
atrophy, and vacuolation were each scored in a blinded manner. Reported P values 
are two-sided.
RESULTS: Persons harboring cagA+ strains (n = 20) had significantly higher 
gastric epithelial proliferation scores than persons infected with cagA-strains 
(n = 9) or uninfected persons (n = 21) (P = .025 and P<.001, respectively), but 
the difference in cell proliferation between the latter two groups was not 
statistically significant. The number of apoptotic cells per 100 epithelial 
cells (apoptotic index) in persons infected with cagA+ strains was lower than in 
persons infected with cagA-strains (P = .05). Apoptotic indices in the cagA+ 
group were similar to those in the uninfected group (P = .2). Epithelial cell 
proliferation was significantly correlated with acute gastric inflammation, but 
only in the cagA+ group (r = .44; P = .006). The cagA+ and vacA s1a genotypes 
were found to be concordant, confirming the close relationship between these 
virulence-related genotypes.
CONCLUSIONS: Gastric mucosal proliferation was significantly correlated with the 
severity of acute gastritis in persons infected with cagA+ vacA s1a strains of 
H. pylori. This increased proliferation was not accompanied by a parallel 
increase in apoptosis.
IMPLICATIONS: Increased cell proliferation in the absence of a corresponding 
increase in apoptosis may explain the heightened risk for gastric carcinoma that 
is associated with infection by cagA+ vacA s1a strains of H. pylori.