E-cadherin gene mutations in human intrahepatic cholangiocarcinoma.
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.
Second Department of Pathology, Tottori University, Faculty of Medicine, 86 Nishi-cho, Yonago 683-8503, Tottori, Japan.
K
K
Endo
K
K
Ashida
N
N
Miyake
T
T
Terada
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D015820:Cadherins; D009363:Neoplasm Proteins