Intracellular, intercellular and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by H. pylori.

Background & Aims: It is not clear how Helicobacter
pylori, an apparently extracellular pathogen colonizing
the luminal side of the gastric epithelium, invariably
causes an immune-inflammatory response on the stromal
side of the mucosa. Penetration of H pylori into
epithelial cell lines and its interaction with immuneinflammatory
cells have been documented in vitro.
Several investigations also showed in vivo bacterial penetration
into the epithelium up to the lamina propria;
however, the identification as H pylori of the bacterialike
bodies observed in unchanged, metaplastic, or neoplastic
mucosa remained sometimes questionable.
Methods: To search for bacteria-like organisms, we
used transmission electron microscopy on endoscopic
biopsy specimens from 20 dyspeptic subjects
and surgical specimens of neoplastic and nonneoplastic
mucosa from 20 cancerous stomachs. To ascertain
the H pylori nature of the organisms found, we
used 6 different antibodies directed against bacterial
lysates, purified vacuolating cytotoxin A, or purified
cytotoxin-associated antigen A in immunogold tests.
The results were compared with those of H pylori
strains cultivated in vitro. Results: In nonmetaplastic
gastric epithelium, cytochemically proven H pylori
were detected, in the majority of cases, inside cytoplasm
of epithelial cells, in intraepithelial intercellular
spaces, and in underlying lamina propria, often in
direct contact with immune-inflammatory cells and
sometimes inside small blood vessels. Cytochemically
proven H pylori were also observed inside 6
of 8 intestinal metaplasias and 9 of 20 cancers.
Conclusions: H pylori penetrates normal, metaplastic,
and neoplastic gastric epithelium in vivo,
intracellularly, or interstitially to cause a strong
immune-inflammatory response and promote gastric
carcinogenesis.