Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas
Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas
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DOI：
10.1016/j.jhep.2004.04.030
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发表时间：
2004-08-01
影响因子：
25.7
通讯作者：
Zucman-Rossi, J
中科院分区：
文献类型：
--
作者：
Cazals-Hatem, D;Rebouissou, S;Zucman-Rossi, J
背景/目的：肝细胞-胆管细胞癌（HCC-CC）表现为肝细胞和胆管上皮的双重分化。为了更好地了解胆管癌（CC），HCC-CC和肝细胞癌（HCC）之间的关系，我们筛选的遗传alternations.Methods：一系列的9 CC，15 HCC-CC和3个分离的HCC和CC病变（“碰撞肿瘤”）进行了筛选杂合性缺失（洛合性缺失），使用400个微卫星标记和p53和β-连环蛋白突变。一个比较与以前的特点系列的137 HCC performed.Results：在6例CC和HCC-CC，我们确定TP 53基因突变。CTNNB 1/β-catenin在两名碰撞肿瘤患者中被鉴定，但在CC或HCC-CC中未发现突变。CC和HCC-CC均存在高度的染色体不稳定性，在50%以上的CC和HCC-CC病例中发现3 p和14 q的复发性特异性洛缺失，而在10%以下的HCC病例中发现这些染色体区域的缺失（p < 10（-5））。最小共同缺失区（MCRD）分别位于3 p24-p14和14 q24-q32。结论：混合型肝癌与原发性肝癌在遗传学上更接近于原发性肝癌，两者共同的致癌途径可能发生改变。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Combined hepatocellular-cholangiocarcinoma (HCC-CC) show dual hepatocellular and biliary epithelial differentiation. To better understand the relations between cholangiocarcinoma (CC), HCC-CC and hepatocellular carcinoma (HCC), we screened for genetic alterations.Methods: A series of nine CC, 15 HCC-CC and three separated HCC and CC lesions ('collision tumors') were screened for loss of heterozygosity (LOH) using 400 microsatellite markers and for p53 and beta-catenin mutations. A comparison with a previously characterized series of 137 HCC was performed.Results: In six cases of CC and HCC-CC, we identified TP53 gene mutations. A CTNNB1/beta-catenin was identified in two patients presenting collision tumors, but no mutations were found in CC or in HCC-CC. A high level of chromosome instability in both CC and HCC-CC was found. Recurrent specific LOH were identified at 3p and 14q in more than 50% of the CC and the HCC-CC cases, whereas these chromosomal regions were deleted in less than 10% of the HCC cases (p < 10(-5)). Minimal common regions of deletion (MCRD) were defined at 3p24-p14 and 14q24-q32, respectively.Conclusions: These results suggest that combined HCC-CC are genetically closer to CC than HCC and common carcinogenesis pathways may be altered in HCC-CC and CC. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.