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.
J Hepatol. 2001 Aug;35(2):235-44. doi: 10.1016/s0168-8278(01)00106-4.
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.
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.
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.
These results suggest that mdm-2 plays a role, which might be partially through inhibiting p53 activity, in cholangiocarcinogenesis and that M
背景/目的：肝内胆管癌（ICC）起源于肝内胆管上皮，是原发性肝癌中第二常见的类型。本研究的目的是阐明胆管癌发生的机制。
我们研究了人类ICC组织中涉及8个高度多态性微卫星标记的微卫星不稳定性（MSI）发生率以及K-ras、p53和mdm-2基因的改变。还通过免疫组织化学研究了mdm-2癌蛋白的过表达情况。
在所有检测的65例病例中，3例（4.6%）在密码子12处发现K-ras基因突变。对28例病例进行了p53改变分析，其中包括22例冷冻样本，3例（10.7%）发现突变。在分析的60例病例中，25例（41.7%）观察到mdm-2蛋白过表达。在22例冷冻样本中，7例（31.8%）显示mdm-2扩增，4例（18.2%）显示MSI阳性表型。在分析的病例中，所有mdm-2扩增/过表达的肿瘤均携带野生型p53基因，所有微卫星不稳定性阳性病例均来自肿块形成（MF）+导管周围浸润（PI）亚型。
这些结果表明，mdm-2在胆管癌发生中起作用，可能部分通过抑制p53活性，并且M
