E-cadherin gene mutations are rare in adenocarcinomas of the oesophagus

Reduced expression of E-cadherin, a cell-cell adhesion molecule, is observed in oesophageal adenocarcinomas and correlates with less favourable pathological parameters and survival. To determine if genetic events lead to reduced E-cadherin expression in these patients, we screened all 16 exons of the E-cadherin gene for mutations with the polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) technique in 49 resection specimens, including four loco-regional lymph node metastases, four established cell lines and four xenografts. Fifteen exon-spanning primer pairs were used, and in nine amplicons aberrant bands were detected. Sequencing of the amplicons revealed a one base-pair deletion (codon 120; exon 3) in cell lines JROECL 47 and JROECL 50 leading to a premature downstream stop codon. Polymorphisms were identified for amplicons 1, 4/5, 11, 12, 13, 14 and 16 corresponding with data from the literature. Three new polymorphisms were detected for amplicons 2, 3 and 4/5. Loss of heterozygosity (LOH) of the E-cadherin locus on 16q22.1 was examined with four polymorphic markers. LOH was found in 31 of the 48 informative cases (65%). These results show that, despite the frequent LOH of the E-cadherin locus, mutations in the E-cadherin gene are rare events and can not be held responsible for down-regulation of E-cadherin observed in the majority of adenocarcinomas of the oesophagus.