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K-ras mutations and cell kinetics in Helicobacter pylori associated gastric intestinal metaplasia: a comparison before and after eradication in patients with chronic gastritis and gastric cancer
  1. J Watari1,
  2. A Tanaka1,
  3. H Tanabe1,
  4. R Sato1,
  5. K Moriichi1,
  6. A Zaky1,
  7. K Okamoto1,
  8. A Maemoto1,
  9. M Fujiya1,
  10. T Ashida1,
  11. K M Das2,
  12. Y Kohgo1
  1. 1Division of Gastroenterology and Hepatology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan
  2. 2Crohn’s and Colitis Center of New Jersey, Division of Gastroenterology and Hepatology, Department of Medicine and Pathology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
  1. Correspondence to:
 Dr J Watari
 Division of Gastroenterology and Hepatology, Department of Medicine, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan; jiro{at}


Background:Helicobacter pylori related gastric intestinal metaplasia (IM) is considered to be a precancerous lesion.

Aims: To identify the effects of H pylori eradication on K-ras mutations, cell kinetics in IM and histological changes in patients with and without gastric cancers in a one-year prospective study.

Methods: Patients included group A (n = 39), chronic gastritis, and group B (n = 53), intestinal-type early gastric cancer patients who had all undergone endoscopic mucosal resection (n = 25) or surgical resection (n = 28). K-ras codon 12 mutations in IM were examined, followed by DNA sequencing analysis. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and using the TUNEL method, respectively.

Results: The incidence of K-ras mutations in the cancer was only 3.8%. The mutant K-ras in IM was observed more frequently in group A (46.2%) than in group B patients (1.9%) (p<0.005). After eradication, the K-ras mutations significantly declined to 12.8% in group A (p<0.005). The mutation pattern of K-ras codon 12 before eradication was that GGT was mainly changed to AGT (50%) in group A. AGT transformation was not affected by treatment. Apoptosis in IM showed an increase after H pylori eradication in both groups (p<0.05 in group A) although no histological improvement in IM was observed. The monocyte score was significantly higher in group A than in group B (p<0.05); the score improved significantly after eradication.

Conclusions: K-ras mutations in IM do not always play a role in gastric carcinogenesis but cell kinetics, especially apoptosis, in IM may contribute to it. There are early events in K-ras mutations which are influenced by H pylori infection; some mutations may also be selected by eradication. These unstable K-ras mutations in IM may be related to lymphocyte infiltration caused by H pylori infection.

  • AI, apoptotic index
  • EMR, endoscopic mucosal resection
  • IM, intestinal metaplasia
  • PI, proliferative index
  • Helicobacter pylori
  • eradication
  • intestinal metaplasia
  • K-ras mutation
  • cell kinetics

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  • Published Online First 22 September 2006

  • Competing interests: None declared.