Frequent hypermethylation of the 5′ CpG island of E-cadherin in esophageal adenocarcinoma

Paul G. Corn, Franz Fogt, Elisabeth I. Heath, Richard Heitmiller, Arlene A. Forastiere, James G. Herman, Tsung Teh Wu

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Purpose: E-cadherin, a Mr 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)2765-2769
Number of pages5
JournalClinical Cancer Research
Volume7
Issue number9
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Corn, P. G., Fogt, F., Heath, E. I., Heitmiller, R., Forastiere, A. A., Herman, J. G., & Wu, T. T. (2001). Frequent hypermethylation of the 5′ CpG island of E-cadherin in esophageal adenocarcinoma. Clinical Cancer Research, 7(9), 2765-2769.