Purpose: E-cadherin, a M-r 120,000 transmembrane glycoprotein, mediates cal
cium-dependent intercellular adhesion that is essential for normal tissue h
omeostasis. 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 mu
tations of the gene (CDH1) are rare.
Experimental Design: In this study, we used a nested PCR approach to examin
e the methylation status of the 5 ' CpG island of E-cadherin in esophageal
specimens obtained from individuals with and without a history of esophagea
Results: In four individuals without esophageal cancer, E-cadherin was comp
letely unmethylated in normal squamous cell-lined esophageal mucosa. In con
trast, in patients with esophageal adenocarcinoma, E-cadherin was methylate
d in 26 of 31 (84%) tumor specimens. In the majority of cases, matched norm
al tissue (esophagus or stomach) from each patient was completely unmethyla
ted. By immunostaining, methylated tumor samples demonstrated heterogeneous
ly decreased membranous E-cadherin staining.
Conclusions: These data suggest that epigenetic silencing via aberrant meth
ylation of the E-cadherin promoter is a common cause of inactivation of thi
s gene in esophageal adenocarcinoma.