title: Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma.
abstract: OBJECTIVE
  E-cadherin, a M(r) 120,000 transmembrane glycoprotein, mediates calcium-dependent intercellular adhesion that is essential for normal tissue homeostasis. Loss of E-cadherin occurs in a variety of epithelial tumors and is correlated with invasion and metastasis. In esophageal adenocarcinoma, reduction of E-cadherin expression has been demonstrated previously, but mutations of the gene (CDH1) are rare.
  
  
  METHODS
  In this study, we used a nested PCR approach to examine the methylation status of the 5' CpG island of E-cadherin in esophageal specimens obtained from individuals with and without a history of esophageal cancer.
  
  
  RESULTS
  In four individuals without esophageal cancer, E-cadherin was completely unmethylated in normal squamous cell-lined esophageal mucosa. In contrast, in patients with esophageal adenocarcinoma, E-cadherin was methylated in 26 of 31 (84%) tumor specimens. In the majority of cases, matched normal tissue (esophagus or stomach) from each patient was completely unmethylated. By immunostaining, methylated tumor samples demonstrated heterogeneously decreased membranous E-cadherin staining.
  
  
  CONCLUSIONS
  These data suggest that epigenetic silencing via aberrant methylation of the E-cadherin promoter is a common cause of inactivation of this gene in esophageal adenocarcinoma.
authors.affiliation: University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA. pcorn@mail.med.upenn.edu
authors.forename: P G
authors.initials: PG
authors.lastname: Corn
authors.forename: E I
authors.initials: EI
authors.lastname: Heath
authors.forename: R
authors.initials: R
authors.lastname: Heitmiller
authors.forename: F
authors.initials: F
authors.lastname: Fogt
authors.forename: A A
authors.initials: AA
authors.lastname: Forastiere
authors.forename: J G
authors.initials: JG
authors.lastname: Herman
authors.forename: T T
authors.initials: TT
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D004273:DNA, Neoplasm