Kishimoto Y, Shiota G, Kamisaki Y, Wada K, Nakamoto K, Yamawaki M, Kotani M, Itoh T, Kawasaki H
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
Oncology. 1997 Jul-Aug;54(4):304-10. doi: 10.1159/000227708.
The incidence of p53 gene aberrations is reported to be about 20-50% in hepatocellular carcinomas (HCCs). In most cases, HCC is clinically preceded by liver cirrhosis, but the genetic changes in cirrhosis are not known well. Therefore, we studied the loss of heterozygosity (LOH) of the p53 gene in cirrhotic and neoplastic foci in the livers of patients with HCC. To assess the relationship between the LOH status of the p53 gene in the liver cirrhosis stage and that in HCC, we analyzed the samples microdissected from paraffin-embedded tissues using the polymerase-chain-reaction-based assay. We studied 18 patients with HCC. Fourteen of the 18 cases showed constitutional heterozygosity for the microsatellite markers. In 8 (57%) of the 14 informative cases, LOH was detected in primary HCCs. Among these 8 doubly informative (informative and LOH positive in primary HCC) cases, 5 cases (63%) showed LOH in liver cirrhosis lesions. The pattern of p53 allelic loss in the cirrhotic foci was identical with that in the corresponding tumor. The remaining 6 cases without LOH of the p53 gene in HCC showed on p53 loss in any cirrhotic foci. LOH of the p53 gene may occur before the development of HCC.
据报道，在肝细胞癌（HCC）中，p53基因畸变的发生率约为20%-50%。在大多数情况下，HCC临床上先于肝硬化出现，但肝硬化中的基因变化尚不清楚。因此，我们研究了HCC患者肝脏中肝硬化病灶和肿瘤病灶中p53基因的杂合性缺失（LOH）情况。为了评估肝硬化阶段和HCC中p53基因LOH状态之间的关系，我们使用基于聚合酶链反应的检测方法，分析了从石蜡包埋组织中显微切割得到的样本。我们研究了18例HCC患者。18例中有14例在微卫星标记上显示出组成型杂合性。在这14例有信息价值的病例中，8例（57%）在原发性HCC中检测到LOH。在这8例双重有信息价值（有信息价值且原发性HCC中LOH阳性）的病例中，5例（63%）在肝硬化病灶中显示出LOH。肝硬化病灶中p53等位基因缺失的模式与相应肿瘤中的模式相同。其余6例HCC中无p53基因LOH的病例在任何肝硬化病灶中均未显示p53缺失。p53基因的LOH可能在HCC发生之前就已出现。
