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


OBJECTIVE
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.
Watari
J
J
Division of Gastroenterology and Hepatology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan. jiro@asahikawa-med.ac.jp
Tanaka
A
A
Tanabe
H
H
Sato
R
R
Moriichi
K
K
Zaky
A
A
Okamoto
K
K
Maemoto
A
A
Fujiya
M
M
Ashida
T
T
Das
K M
KM
Kohgo
Y
Y
D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002908:Chronic Disease; D003062:Codon / Q000235:genetics; D005756:Gastritis / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D011905:Genes, ras / Q000235:genetics*; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008679:Metaplasia / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D009154:Mutation; D009504:Neutrophils / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D011446:Prospective Studies; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology / Q000473:pathology*
D003062:Codon