E-cadherin gene mutations in human intrahepatic cholangiocarcinoma

Deletions or mutations of the E-cadherin gene may result in reduced cell ad hesiveness. In particular, conservative point mutations within the N-termin al calcium-binding pocket (including exons 7, 8, and 9) are frequently dete cted in several cancers and are enough to abolish cell-cell adhesion. There have been no studies on E-cadherin gene mutations in human intrahepatic ch olangiocarcinoma (TCC), Human ICCs were therefore investigated for E-cadher in gene mutations within exons 7, 8, and 9, In addition, the relationships were analysed between their mutations and the immunohistochemical expressio n of E-cadherin, histological grade, and clinicopathological parameters, Th e E-cadherin gene was analysed in 31 tumours by nested polymerase chain rea ction/single-strand conformation polymorphism (PCR/SSCP) follow fd by DNA s equencing, in four of the 34 cases (11.8%), tumour-restricted mobility shif ts were observed; two cases harboured a single shift, one case presented tw o different mobility shifts, and one case presented three different mobilit y shifts within eons 7 and 8, encoding extracellular domains of E-cadherin. Polymorphism as previously reported was not identified and ail seven nem D NA alterations were not present in genomic DNA of non-tumour origin, The E- cadherin gene mutations correlated significantly with down-regulated E-cadh erin protein expression and high ICC histological grade. These data suggest that E-cadherin gene mutations in ICC are associated with reduced cell adh esiveness and high histological grade. Copyright (C) 2000 John Wiley & Sons , Ltd.