TY - JOUR
T1 - E-cadherin gene mutations in human intrahepatic cholangiocarcinoma
AU - Endo, Kanenori
AU - Ashida, Keigo
AU - Miyake, Noriko
AU - Terada, Tadashi
PY - 2001/4/2
Y1 - 2001/4/2
N2 - 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.
AB - 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.
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U2 - 10.1002/1096-9896(2000)9999:9999<::AID-PATH816>3.0.CO;2-K
DO - 10.1002/1096-9896(2000)9999:9999<::AID-PATH816>3.0.CO;2-K
M3 - Article
C2 - 11241409
AN - SCOPUS:0035093749
VL - 193
SP - 310
EP - 317
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 3
ER -