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

Reduced expression of E-cadherin, a cell-cell adhesion molecule, is observe d in oesophageal adenocarcinomas and correlates with less favourable pathol ogical parameters and survival. To determine if genetic events lead to redu ced E-cadherin expression in these patients, we screened all 16 exons of th e E-cadherin gene for mutations with the polymerase chain reaction single-s trand conformation polymorphism analysis (PCR-SSCP) technique in 49 resecti on specimens, including four loco-regional lymph node metastases, four esta blished cell lines and four xenografts. Fifteen exon;spanning primer pairs were used, and in nine amplicons aberrant bands were detected. Sequencing o f the amplicons revealed a one base-pair deletion (codon 120; exon 3) in ce ll lines JROECL 47 and JROECL 50 leading to a premature downstream stop cod on. Polymorphisms were identified for amplicons 1,4/5, 11, 12, 13, 14 and 1 6 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-cadhe rin gene are rare events and can not be held responsible for dawn-regulatio n of E-cadherin observed in the majority of adenocarcinomas of the oesophag us.