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

Citation
Pg. Corn et al., Frequent hypermethylation of the 5 ' CpG island of E-cadherin in esophageal adenocarcinoma, CLIN CANC R, 7(9), 2001, pp. 2765-2769
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2765 - 2769
Database
ISI
SICI code
1078-0432(200109)7:9<2765:FHOT5'>2.0.ZU;2-C
Abstract
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 l cancer. 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.