P53 PROTEIN ACCUMULATION IN EUROPEAN HEPATOCELLULAR-CARCINOMA IS NOT ALWAYS DEPENDENT ON P53 GENE MUTATION
P53 PROTEIN ACCUMULATION IN EUROPEAN HEPATOCELLULAR-CARCINOMA IS NOT ALWAYS DEPENDENT ON P53 GENE MUTATION
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DOI：
10.1016/0016-5085(95)90217-1
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发表时间：
1995-04-01
期刊：
影响因子：
29.4
通讯作者：
DEBUIRE, B
中科院分区：
文献类型：
--
作者：
BOURDON, JC;DERRICO, A;DEBUIRE, B
背景/目的：p53蛋白的免疫组化反应在各种人类恶性肿瘤中很常见，并且通常与p53基因突变有关。然而，在一些肿瘤类型中，已经显示野生型p53的积累。之前，我们使用免疫组织化学分析了96例欧洲肝细胞癌，发现其中31%的肿瘤在细胞核中过表达p53。本研究的目的是确定p53阳性是否与欧洲肝细胞癌中存在的结构性p53基因异常相关。研究方法：从冰冻切片中提取20个肿瘤的DNA，其中10个具有强免疫染色，10个具有不可检测的p53染色，并对p53基因的整个编码部分进行测序。结果：10例高表达p53蛋白的肿瘤中有5例出现错义点突变。其余5例p53水平高的肿瘤显示野生型编码序列。在10个含有不可检测水平的p53蛋白的肿瘤中，有一个在内含子4的剪接受体位点有1个碱基对缺失。结论：结果强烈表明，在欧洲肝细胞癌中，p53蛋白的稳定依赖于p53基因突变以外的因素，如与细胞或病毒来源的其他分子结合。
Background/Aims: Immunohistochemical reactivity for p53 protein is; common in various human malignancies and often related to p53 gene mutation. However, in some tumor types, accumulation of wild-type p53 has been shown. previously, we analyzed 96 European hepatocellular carcinomas using immunohistochemistry and found that 31% of these tumors overexpressed p53 in the cell nucleus. the aim of the present study was to establish whether p53 positivity correlates with the presence of structural p53 gene abnormalities in European hepatocellular carcinoma. Methods: DNA from 20 tumors, 10 with strong immunostaining and 10 with undetectable staining for p53, was extracted from frozen sections, and the entire coding portion of the p53 gene was sequenced. Results: Five of the 10 tumors containing high levels of p53 protein showed missense point mutations. The remaining 5 tumors with high p53 levels showed the wild-type coding sequence. One of the 10 tumors containing undetectable levels of p53 protein had a 1-base pair deletion in the splice acceptor site of intron 4. Conclusions: The results strongly suggest that, in European hepatocellular carcinomas, stabilization of the p53 protein depends on factors other than p53 gene mutation, such as binding to other molecules of cellular or viral origin.