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E‐cadherin gene mutations in human intrahepatic cholangiocarcinoma
Author(s) -
Endo Kanenori,
Ashida Keigo,
Miyake Noriko,
Terada Tadashi
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(2000)9999:9999<::aid-path816>3.0.co;2-k
Subject(s) - cadherin , exon , biology , gene , microbiology and biotechnology , point mutation , single strand conformation polymorphism , mutation , gene mutation , genetics , cancer research , cell
Deletions or mutations of the E‐cadherin gene may result in reduced cell adhesiveness. In particular, conservative point mutations within the N‐terminal calcium‐binding pocket (including exons 7, 8, and 9) are frequently detected in several cancers and are enough to abolish cell–cell adhesion. There have been no studies on E‐cadherin gene mutations in human intrahepatic cholangiocarcinoma (ICC). Human ICCs were therefore investigated for E‐cadherin gene mutations within exons 7, 8, and 9. In addition, the relationships were analysed between their mutations and the immunohistochemical expression of E‐cadherin, histological grade, and clinicopathological parameters. The E‐cadherin gene was analysed in 34 tumours by nested polymerase chain reaction/single‐strand conformation polymorphism (PCR/SSCP) followed by DNA sequencing. In four of the 34 cases (11.8%), tumour‐restricted mobility shifts were observed; two cases harboured a single shift, one case presented two different mobility shifts, and one case presented three different mobility shifts within exons 7 and 8, encoding extracellular domains of E‐cadherin. Polymorphism as previously reported was not identified and all seven new DNA alterations were not present in genomic DNA of non‐tumour origin. The E‐cadherin gene mutations correlated significantly with down‐regulated E‐cadherin protein expression and high ICC histological grade. These data suggest that E‐cadherin gene mutations in ICC are associated with reduced cell adhesiveness and high histological grade. Copyright © 2000 John Wiley & Sons, Ltd.