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 language||English (US)|
|Number of pages||5|
|Journal||Clinical Cancer Research|
|State||Published - 2001|
ASJC Scopus subject areas
- Cancer Research