J Hepatol  2001 Aug;35(2):235-44 

Microsatellite instability and alternative genetic pathway in intrahepatic
cholangiocarcinoma.

Momoi H, Itoh T, Nozaki Y, Arima Y, Okabe H, Satoh S, Toda Y, Sakai E,
Nakagawara K, Flemming P, Yamamoto M, Shimahara Y, Yamaoka Y, Fukumoto M.

Department of Gastroenterological Surgery, Kyoto University Graduate School of
Medicine, Japan.

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

PMID: 11580146 [PubMed - indexed for MEDLINE]