title: Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein.
abstract: BACKGROUND
  Helicobacer pylori infection is a major gastric cancer risk factor. Deficient DNA mismatch repair (MMR) caused by H. pylori may underlie microsatellite instability (MSI) in the gastric epithelium and may represent a major mechanism of mutation accumulation in the gastric mucosa during the early stages of H. pylori-associated gastric carcinogenesis. In this study, we examined the expression of DNA MMR protein (hMLH1 and hMSH2) in patients with chronic H. pylori infection before and after eradication of the infection.
  
  
  METHODS
  Gastric tissue samples were collected from 60 patients with H. pylori gastritis and peptic ulcer disease before and after eradication of the infection. The DNA MMR protein expression (hMLH1 and hMSH2) was determined by immunohistochemical staining in 60 patients before and after H. pylori eradication. The percentage of epithelial cell nuclei and intensity of staining were then compared in gastric biopsies before and after eradication.
  
  
  RESULTS
  The percentage of hMLH1 (76.60 +/- 20.27, 84.82 +/- 12.73, p=.01) and hMSH2 (82.36 +/- 12.86, 88.11 +/- 9.27, p<.05) positive epithelial cells significantly increased in 53 patients who became H. pylori-negative after eradication therapy. However, the intensity of hMLH1 and hMSH2 staining was not significantly different. In those 7 patients, who did not respond to the eradication therapy and were still H. pylori-positive, the percent positivity and intensity of hMLH1 and hMSH2 staining did not change.
  
  
  CONCLUSIONS
  The expression of DNA MMR proteins increased in the gastric mucosa after H. pylori eradication, indicating that H. pylori gastritis may be associated with a reduced DNA MMR system during infection. The effect of H. pylori infection on MMR protein expression appears to be at least partially reversible after H. pylori eradication. These data suggest that H. pylori gastritis might lead to a deficiency of DNA MMR in gastric epithelium that may increase the risk of mutation accumulation in the gastric mucosa cells during chronic H. pylori infection.
authors.affiliation: Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Park
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Park
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jeong Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Yong Kyun
authors.initials: YK
authors.lastname: Cho
authors.forename: Hong Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chong Il
authors.initials: CI
authors.lastname: Sohn
authors.forename: Woo Kyu
authors.initials: WK
authors.lastname: Jeon
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Kim
authors.forename: Eun Yoon
authors.initials: EY
authors.lastname: Cho
authors.forename: Eo-Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Seoung Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Sung
authors.forename: Antonia R
authors.initials: AR
authors.lastname: Sepulveda
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D002908:Chronic Disease; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005756:Gastritis / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010437:Peptic Ulcer / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein