Amplification of c-myc in hepatocellular carcinoma:: Correlation with clinicopathologic features, proliferative activity and p53 overexpression
Amplification of c-myc in hepatocellular carcinoma:: Correlation with clinicopathologic features, proliferative activity and p53 overexpression
复制标题
DOI：
10.1159/000012024
复制
发表时间：
1999-01-01
期刊：
影响因子：
3.5
通讯作者：
Morishita, Y
中科院分区：
文献类型：
--
作者：
Kawate, S;Fukusato, T;Morishita, Y
原癌基因c-myc的表达与肝再生和肝癌发生有关。然而，c-myc基因扩增在人肝细胞癌中的生物学意义尚未得到证实。我们将c-myc基因扩增与42例切除肿瘤的临床病理特征、增殖活性和p53表达相关联。使用差异聚合酶链反应测定肿瘤组织中的c-myc扩增，这是一种用于评价存档福尔马林固定石蜡包埋组织中基因扩增的有用程序，与多巴胺D2受体基因进行比较。通过嗜银核仁组成区的数量和使用抗Ki-67单克隆抗体的免疫组化核标记率来估计增殖活性。c-myc基因在42例肿瘤中有14例（33.3%）扩增。c-myc扩增在年轻患者、较大肿瘤和低分化肿瘤中更常见。甲胎蛋白水平或病毒性肝炎状态无相关性。扩增与细胞增殖活性和p53过表达呈正相关。显示c-myc扩增的患者的无病生存期明显短于无扩增的患者。这些结果表明，c-myc扩增是肝细胞癌恶性潜力和预后不良的指标。c-myc扩增和p53改变可能共同参与了这些肿瘤的进展。
Expression of the proto-oncogene c-myc has been implicated in liver regeneration and hepatocarcinogenesis. The biologic significance of c-myc gene amplification in human hepatocellular carcinoma, however, is unconfirmed. We correlated c-myc gene amplification with clinicopathologic features, proliferative activity, and p53 expression in 42 resected tumors. c-myc amplification in tumor tissue was determined using a differential polymerase chain reaction, a useful procedure for the evaluation of gene amplification in archival formalin-fixed paraffin-embedded tissues, in comparison with a dopamine D2 receptor gene. Proliferative activity was estimated by numbers of argyrophilic nucleolar organizer regions and immunohistochemical nuclear labeling rates using a monoclonal antibody against Ki-67. The c-myc gene was amplified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. No correlation was noted with a-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplification. These results suggest that c-myc amplification is an indicator of malignant potential and poor prognosis in hepatocellular carcinoma. c-myc amplification and p53 alteration may be coparticipating events in the progression of these tumors.