ORIGINAL ARTICLE

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

J Watari¹, A Tanaka¹, H Tanabe¹, R Sato¹, K Moriichi¹, A Zaky¹, K Okamoto¹, A Maemoto¹, M Fujiya¹, T Ashida¹, K M Das², Y Kohgo¹

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan
² Crohn’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

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}asahikawa-med.ac.jp

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.

Abbreviations: AI, apoptotic index; EMR, endoscopic mucosal resection; IM, intestinal metaplasia; PI, proliferative index

Keywords: Helicobacter pylori; eradication; intestinal metaplasia; K-ras mutation; cell kinetics

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