Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma
Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma
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DOI：
10.1053/hupa.2002.127444
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发表时间：
2002-09-01
期刊：
影响因子：
3.3
通讯作者：
Jang, JJ
中科院分区：
文献类型：
--
作者：
Kang, YK;Kim, WH;Jang, JJ
G1-S细胞周期阻滞和tgf - β /Smad通路异常是人类癌变的关键事件。我们通过免疫组化染色研究了42例肝内胆管癌（ICCs）中p53、p16、p27、cyclin D1、Rb和Smad4/Dpc4这两条通路的变化。p53和cyclin D1核异常过表达分别为15例（35.7%）和26例（61.9%）。p16、p27、Rb和Smad4的全部缺失分别在15例（35.7%）、13例（31.0%）、5例（11.9%）和19例（45.2%）中检测到。40例（95.2%）至少出现一条通路异常，其中21例（50%）仅出现G1-S通路异常，17例（40.5%）同时出现两条通路异常，2例（4.8%）仅出现tgf - β /Smad通路异常。在所检测的基因中，Smad4缺失与pTNM分期呈正相关（P < 0.05）。高改变组（2 ~ 5个基因改变，n = 29）的总分期明显高于低改变组（1个或无基因改变，n = 13） （P < 0.01）。我们还检测了上述基因在伴随的胆道发育不良中的表达，发现13例发育不良病变中有7例p53、cyclin D1或p16表达异常。我们的数据表明，G1-S细胞周期异常和tgf - β /Smad通路改变是胆管癌发生的主要事件。此外，检查基因的改变可能对可切除的icc患者的临床结果产生累积效应。2002版权所有，爱思唯尔科学（美国）。版权所有。
Aberrations of G1-S cell cycle arrest and TGF-beta/Smad pathway are critical events in human carcinogenesis. We studied alterations of both pathways by immunohistochemical staining for p53, p16, p27, cyclin D1, Rb and Smad4/Dpc4 in 42 intrahepatic cholangiocarcinomas (ICCs). Abnormal nuclear overexpression of p53 and cyclin D1 was noted in 15 (35.7%) and 26 (61.9%) cases, respectively. Total loss of p16, p27, Rb and Smad4 was detected in 15 (35.7%), 13 (31.0%), 5 (11.9%) and 19 (45.2%) cases, respectively. Forty cases (95.2%) showed aberrations of at least one of the pathways, of which 21 (50%) revealed abnormality in G1-S pathway only, 17 (40.5%) had abnormalities in both pathways and 2 (4.8%) had an abnormality in TGF-beta/Smad pathway only. Among the examined genes, loss of Smad4 was found to have a positive relationship with the pTNM stage (P < 0.05). The overall stage of the high-altered group (alterations in 2 to 5 of the genes, n = 29) was significantly higher than that of the low-altered group (alteration of one or no gene, n = 13) (P < 0.01). We also examined the expression of above genes in the accompanying biliary dysplasia and found out abnormal expression of p53, cyclin D1 or p16 in 7 out of 13 dysplastic lesions. Our data suggest that abnormal G1-S cell cycle and altered TGF-beta/Smad pathway are major events in cholangiocarcinogenesis. Moreover, there might be a possible cumulative effect of the alterations in the examined genes upon the clinical outcome of patients with resectable ICCs. Hum Copyright 2002, Elsevier Science (USA). All rights reserved.