title: Intracellular, intercellular, and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by Helicobacter pylori.
abstract: OBJECTIVE
  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 immune-inflammatory 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 bacteria-like 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.
authors: Department of Human Pathology, University of Pavia, Pavia, Italy.
authors: Vittorio
authors: V
authors: Necchi
authors: Maria Elena
authors: ME
authors: Candusso
authors: Francesca
authors: F
authors: Tava
authors: Ombretta
authors: O
authors: Luinetti
authors: Ulderico
authors: U
authors: Ventura
authors: Roberto
authors: R
authors: Fiocca
authors: Vittorio
authors: V
authors: Ricci
authors: Enrico
authors: E
authors: Solcia
mesh_terms: D000907:Antibodies, Bacterial; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001706:Biopsy; D016099:Endoscopy, Gastrointestinal; D005753:Gastric Mucosa / Q000382:microbiology* / Q000648:ultrastructure; D016481:Helicobacter Infections / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007365:Intercellular Junctions / Q000382:microbiology / Q000648:ultrastructure; D007414:Intestinal Neoplasms / Q000382:microbiology* / Q000648:ultrastructure; D008679:Metaplasia; D046529:Microscopy, Electron, Transmission / Q000379:methods; D011230:Precancerous Conditions / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000648:ultrastructure; D017154:Stromal Cells / Q000382:microbiology* / Q000648:ultrastructure
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori