Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma

Am J Pathol. 1997 Sep;151(3):821-9.


Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / complications
  • Adenocarcinoma / pathology*
  • Aged
  • Cell Division
  • DNA Damage*
  • Female
  • Gastric Mucosa / chemistry
  • Gastric Mucosa / pathology*
  • Helicobacter Infections / complications
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / isolation & purification
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Male
  • Middle Aged
  • Pancreatic Elastase / analysis
  • Stomach Neoplasms / chemistry
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / pathology*


  • Ki-67 Antigen
  • Pancreatic Elastase