Expression of cell-cycle related proteins in Helicobacter pylori gastritis and association with gastric carcinoma

Neoplasma. 2002;49(2):95-100.


Helicobacter pylori (H. pylori) infection is associated with changes in epithelial turnover, through their significance of these in gastric carcinogenesis is still controversial. The purpose of this study was to determine the influence of H. pylori infection on cell proliferation and the relation with the cell-cycle regulators, and finally to provide insights into the mechanism by which H. pylori may lead to gastric carcinogenesis. We investigated Ki-67, p53, p21(Waf1/Cip1), cyclin D1 expression in 55 patients with H. pylori gastritis, and compared the results with patients those of non-H. pylori gastritis patients (n=21), gastric adenocarcinoma patients (n=8) and samples with normal gastric mucosa (n=12). Gastric biopsies were histologically evaluated for inflammatory reaction, intestinal metaplasia and atrophy according to the Sydney system. Overexpression of Ki-67, p53, p21(Waf1/Cip1) and cyclin D1 was found in H. pylori gastritis patients (32.7%, 10.9%, 20.0% and 7.3%, respectively), whereas only scattered expression in cells in the neck region of the crypts, but no overexpression was found in gastric antral epithelial cells in biopsy specimens from patients with non-H. pylori gastritis and noninflammed mucosa. A significant relationship was found between the grade of H. pylori colonization and Ki-67, p53, p21(Waf1/Cip1) and cyclin D1 expression. Expression was significantly higher in patients with intestinal metaplasia with atrophy, whereas no overexpression was found in patients without intestinal metaplasia with atrophy (p=0.05). H. pylori infection is associated with increased cell proliferation, increased epithelial DNA damage, and atrophy, which might contribute to the development of gastric cancer. Even if the exact mechanism has not been elucidated yet, our results suggest that H. pylori infection acts as a cofactor in gastric carcinogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / pathology
  • Biopsy
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / biosynthesis*
  • Cell Division
  • Cyclin D1 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • Gastric Mucosa / cytology
  • Gastric Mucosa / pathology
  • Gastritis / complications
  • Gastritis / microbiology*
  • Gastritis / pathology
  • Helicobacter Infections / complications
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / cytology*
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Ki-67 Antigen / biosynthesis*
  • Reference Values
  • Stomach Neoplasms / microbiology*
  • Tumor Suppressor Protein p53 / biosynthesis*


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Ki-67 Antigen
  • Tumor Suppressor Protein p53
  • Cyclin D1