TUMOR SUPPRESSOR GENES IN HUMAN HEPATOCELLULAR CARCINOMA

在肝细胞癌（HCC）中p53突变的研究

Studies of p53 mutations in hepatocellular carcinoma (HCC) have continued. Results from previous studies in this laboratory in patients from China and the U.S. were continued in patients from Europe. p53 expression was studied by immunohistochemical methods in benign and malignant human epithelial liver lesions in 46 patients from Hungary (16 hepatocellular carcinomas, 7 hepatoblastomas, 17 focal nodular hyperplasias, and 6 hepatocellular adenomas). Positive immunostaining for p53 protein, indicating the probable presence of a mutation in the p53 gene, was detected in the nuclei of tumor cells of seven of 16 HCC patients (44%). Immunostaining of p53 was seen in one of seven hepatoblastomas, none of 17 focal nodular hyperplasias, and none of six hepatocellular adenomas, indicating that these other liver lesions probably do not frequently have p53 mutations. In the liver tissue adjacent to all the tumors studied, hepatocytes did not stain for the presumed mutant p53 protein. The detection of mutant p53 in a relatively high percentage of the HCC cases in Hungary, a country in which aflatoxin contamination of the diet is rare, suggests that factors other than aflatoxin led to p53 mutations in these patients. p53 gene mutations appear to be uncommon in hepatoblastoma and benign liver lesions such as focal nodular hyperplasia and hepatocellular adenoma. Studies using single-strand conformation polymorphism (SSCP) and sequencing are being used to identify p53 mutations in HCC patients from Hungary, Korea, and the USA (Texas; NIH; Hawaii). In Korean patients, 14/35 patients (46%) have p53 mutations. In patients from Texas, mutations have been found so far in 3/22 patients (14%), although additional studies are in progress. In addition, wild-type p53 has been cloned to produce reagent materials for other studies, including studying the binding of p53 to cellular proteins and nucleotides.