Document Detail

Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma.
MedLine Citation:
PMID:  11580146     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) arises from intrahepatic bile duct epithelium and is the second most prevalent among primary liver cancers. The aim of this study was to clarify the mechanism of cholangiocarcinogenesis. METHODS: We studied the incidence of microsatellite instability (MSI) involving eight highly polymorphic microsatellite markers and alternations of the K-ras, p53 and mdm-2 genes in human ICC tissues. Overexpression of mdm-2 oncoprotein was also immunohistochemically studied. RESULTS: Of all 65 cases examined, K-ras gene mutation was found in three cases (4.6%) at codon 12. Analysis of p53 alterations was performed in 28 cases including 22 frozen samples and mutations were found in three cases (10.7%). Overexpression of mdm-2 protein was observed in 25 (41.7%) out of 60 cases analyzed. In 22 frozen samples, seven (31.8%) cases showed mdm-2 amplification and four (18.2%) cases revealed MSI-positive phenotype. Among the cases analyzed, all the tumors with mdm-2 amplification/overexpression harbored the wild-type p53 gene and all the microsatellite instability-positive cases were from mass-forming (MF) + periductal-infiltrating (PI) subtype. CONCLUSIONS: These results suggest that mdm-2 plays a role, which might be partially through inhibiting p53 activity, in cholangiocarcinogenesis and that M
H Momoi; T Itoh; Y Nozaki; Y Arima; H Okabe; S Satoh; Y Toda; E Sakai; K Nakagawara; P Flemming; M Yamamoto; Y Shimahara; Y Yamaoka; M Fukumoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  35     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-10-02     Completed Date:  2002-03-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  235-44     Citation Subset:  IM    
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan.
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MeSH Terms
Base Sequence
Bile Duct Neoplasms / etiology,  genetics*,  metabolism,  pathology
Bile Ducts, Intrahepatic*
Cholangiocarcinoma / etiology,  genetics*,  metabolism,  pathology
DNA, Neoplasm / genetics
Gene Expression
Genes, p53
Genes, ras
Microsatellite Repeats*
Middle Aged
Nuclear Proteins*
Polymorphism, Genetic
Proto-Oncogene Proteins / genetics,  metabolism
Proto-Oncogene Proteins c-mdm2
Reg. No./Substance:
0/DNA, Neoplasm; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; EC protein, human; EC Proteins c-mdm2

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