title: [Methylation of p16 and hMLH1 genes in esophageal squamous cell carcinoma and reflux esophagitis].
abstract: OBJECTIVE
  To study the promoter methylation pattern of p16 and hMLH1 genes in esophageal squamous cell carcinoma and reflux esophagitis, and to correlate the results with clinical and pathologic findings.
  
  
  METHODS
  Twelve cases of normal esophagus, 13 cases of esophageal squamous cell carcinoma, 43 cases of reflux esophagitis with basal cell hyperplasia and 21 cases of reflux esophagitis with dysplasia, as confirmed by endoscopic and pathologic examination, were enrolled into the study. Genomic DNA was extracted. The promoter methylation status of p16 was measured by methylation-specific polymerase chain reaction. The promoter methylation status of hMLH1 was measured by sodium bisulfite-restriction enzyme digestion. Immunohistochemical study for p16 and hMLH1 proteins was also carried out.
  
  
  RESULTS
  The rates of p16 methylation in normal esophageal epithelium, basal cell hyperplasia, dysplasia and esophageal squamous cell carcinoma were 0/12, 14.0% (6/43), 38.1% (8/21) and 6/13, respectively. The p16 methylation correlated with the progress of esophageal lesions. On the other hand, the hMLH1 methylation was not observed in the normal esophageal epithelium and reflux esophagitis. One case of esophageal squamous cell carcinoma showed the presence of hMLH1 methylation. The hMLH1 promoter hypermethylation did not correlate with the clinical and pathologic features.
  
  
  CONCLUSIONS
  The p16 methylation may be one of the earliest events in the pathogenesis of esophageal squamous cell carcinoma and is also observed in reflux esophagitis. Reflux esophagitis may be related to the development of esophageal squamous cell carcinoma in Chinese population. In contrast, hMLH1 methylation may not be directly involved in the tumorigenesis of esophageal squamous cell carcinoma.
authors.affiliation: Department of Gastroenterology, Capital Medical University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Xin-ji
authors.initials: XJ
authors.lastname: Xie
authors.forename: Ying-shi
authors.initials: YS
authors.lastname: Piao
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Li-dong
authors.initials: LD
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004942:Esophagitis, Peptic / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005260:Female; D019942:Genes, p16; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019941:Cyclin-Dependent Kinase Inhibitor p16; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1