High-throughput tissue microarray analysis of c-myc activation in chronic liver diseases and hepatocellular carcinoma
High-throughput tissue microarray analysis of c-myc activation in chronic liver diseases and hepatocellular carcinoma
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DOI：
10.1016/j.humpath.2004.06.012
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发表时间：
2004-11-01
期刊：
影响因子：
3.3
通讯作者：
OI-Lin, I
中科院分区：
文献类型：
--
作者：
Chan, KL;Guan, XY;OI-Lin, I
8q23-qter 扩增在人类肝细胞癌 (HCC) 中很常见。 c-myc 是一种位于 8q24 的癌基因，可能在肝癌发生中发挥重要作用。本研究旨在评估肝癌发生中的c-myc激活及其临床病理意义。使用双色荧光原位杂交和免疫组织化学对包含 458 个肝脏样本（包括 HCC、非肿瘤肝脏和正常肝脏）的组织微阵列进行 c-myc 基因扩增和表达的高通量分析。 HCC 表现出频繁的 c-myc 扩增（校正 8 号染色体异型后为 30%）。相比之下，非癌性肝脏（主要是慢性肝炎和肝硬化）没有表现出 c-myc 扩增。尽管 c-myc 扩增，HCC 的核 c-myc 表达量低于慢性肝病肝脏和正常肝脏（分别 P < 0.001 和 0.004）。与患有慢性肝病的肝脏相比，HCC 的细胞质 c-myc 染色也较少（P = 0.002）。然而，尽管没有 c-myc 扩增，但与正常肝脏相比，慢性疾病肝脏的核和细胞质 c-myc 蛋白表达显着增加（分别为 P = 0.015 和 0.009）。临床病理学上，具有静脉渗透和无肿瘤包膜的 HCC 中核 c-myc 的减少更为明显（分别为 P = 0.013 和 0.021），而具有细胞质 c-myc 的 HCC 与较大的肿瘤大小呈正相关（P = 0.027）。 HCC 中 c-myc 扩增与蛋白表达水平之间没有显着相关性。我们的结果表明，慢性肝病中 c-myc 的过度表达可能在肝癌发生的易感性中发挥重要作用。尽管 c-myc 在 HCC 中扩增，但在肝癌发生中 c-myc 激活的独立途径似乎受到严格调节。 (C) 2004 Elsevier Inc. 保留所有权利。
Amplification of 8q23-qter is common in human hepatocellular carcinoma (HCC). c-myc, an oncogene located on 8q24, may be important in hepatocarcinogenesis. The present study aimed to evaluate c-myc activation in hepatocarcinogenesis and its clinicopathological significance. High-throughput analysis of c-myc gene amplification and expression using dual-color fluorescence in situ hybridization and immunohistochemistry was performed on tissue microarrays consisting of 458 liver samples comprising HCCs, nontumorous livers and normal livers. HCCs demonstrated frequent c-myc amplification (30% when corrected for chromosome 8 aneusomy). In contrast, the noncancerous livers, which were mostly chronic hepatitis and cirrhosis, exhibited no c-myc amplification. Despite c-myc amplification, the HCCs exhibited less nuclear c-myc expression than the livers with chronic liver diseases and normal livers (P < 0.001 and 0.004, respectively). The HCCs also had less cytoplasmic c-myc staining than the livers with chronic liver diseases (P = 0.002). Despite their absence of c-myc amplification, however, the livers with chronic disease had significantly increased expression of both nuclear and cytoplasmic c-myc protein compared with normal livers (P = 0.015 and 0.009, respectively). Clinicopathologically, the reduction in nuclear c-myc was more marked in HCCs with venous permeation and absence of tumor encapsulation (P = 0.013 and 0.021, respectively), whereas HCCs with cytoplasmic c-myc were positively associated with larger tumor size (P = 0.027). There was no significant association between c-myc amplification and protein expression levels in HCC. Our results suggest that overexpression of c-myc in chronic liver diseases may play an important role in the predisposition to hepatocarcinogenesis. Although c-myc was amplified in HCC, there appears to be a tight regulation by independent pathways of c-myc activation in hepatocarcinogenesis. (C) 2004 Elsevier Inc. All rights reserved.