Bourdon J C, D'Errico A, Paterlini P, Grigioni W, May E, Debuire B
Centre National de la Recherche Scientifique, Institut de Recherche sur le Cancer, Villejuif, France.
Gastroenterology. 1995 Apr;108(4):1176-82. doi: 10.1016/0016-5085(95)90217-1.
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.
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.
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.
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.
背景/目的：p53蛋白的免疫组化反应性在各种人类恶性肿瘤中很常见，且常与p53基因突变有关。然而，在某些肿瘤类型中，已显示有野生型p53的积累。此前，我们使用免疫组化分析了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在欧洲肝细胞癌中p53阳性是否与p53基因结构异常的存在相关。
从20个肿瘤（10个p53免疫染色强阳性和10个p53染色不可检测）的冰冻切片中提取DNA，并对p53基因的整个编码部分进行测序。
10个含有高水平p53蛋白的肿瘤中有5个显示错义点突变。其余5个p53水平高的肿瘤显示野生型编码序列。10个含有不可检测水平p53蛋白的肿瘤中有1个在内含子4的剪接受体位点有1个碱基对缺失。
结果强烈表明，在欧洲肝细胞癌中，p53蛋白的稳定取决于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。
