TUMOR SUPPRESSOR GENES IN HUMAN HEPATOCELLULAR CARCINOMA

肝细胞癌中P53基因突变的研究 继续。本实验室以前对患者进行的研究结果 来自中国和美国的患者则继续接受来自欧洲的治疗。P53 用免疫组织化学方法研究良性和非小细胞肺癌的表达。 匈牙利46例人恶性上皮性肝脏病变(16例 肝细胞癌、肝母细胞瘤7例、局灶性结节17例 肝细胞腺瘤6例)。免疫阳性染色 对于P53蛋白，表明可能存在突变 在16例肝细胞癌中有7例肿瘤细胞核中检测到P53基因 患者(44%)。7例中有1例P53免疫组织化学染色。 肝母细胞瘤，17例局灶性结节增生性病变中无一例，6例中无一例 肝细胞腺瘤，表明这些其他肝脏病变 可能并不经常有P53突变。在肝组织中 在所有研究的肿瘤旁，肝细胞没有染色 推测为突变型P53蛋白。相对癌组织中突变型P53基因的检测 在匈牙利，肝癌病例比例很高，而在匈牙利，黄曲霉毒素 饮食受到污染的情况很少见，这表明除了 黄曲霉毒素导致这些患者的p53突变。P53基因突变 在肝母细胞瘤和良性肝脏病变中似乎不常见，如 局灶性结节状增生和肝细胞腺瘤。 应用单链构象多态(SSCP)和 正在使用测序来识别肝癌患者中的P53突变 匈牙利、韩国和美国(德克萨斯州；美国国立卫生研究院；夏威夷)。在韩国患者中， 14/35例患者(46%)有P53基因突变。在德克萨斯州的病人中， 到目前为止，在22名患者中发现了3例突变(14%)，尽管 其他研究正在进行中。 此外，还克隆了野生型p53，用于生产试剂材料 用于其他研究，包括研究p53与细胞的结合 蛋白质和核苷酸。

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.