Volkmann M, Müller M, Hofmann W J, Meyer M, Hagelstein J, Räth U, Kommerell B, Zentgraf H, Galle P R
Department of Internal Medicine, University of Heidelberg, Germany.
Hepatology. 1993 Sep;18(3):559-65.
Recently, p53 gene aberrations have been recognized as a relevant factor in hepatocarcinogenesis, in tumors from both high-risk and low-risk areas. Because p53 gene mutations typically result in increased p53 levels in tumor cells, this cellular protein might become immunogenic during tumor development. To test this hypothesis, we have analyzed sera from 80 European patients with hepatocellular carcinoma for the presence of p53 antibodies. For this purpose we developed an immunoblot assay using recombinant p53 as antigen. Sixty-seven sera from patients with different acute and chronic liver diseases were used as controls. In addition, serum alpha-fetoprotein assays were performed. Circulating antibodies against p53 were found in 25% (20 of 80) of the sera from patients with hepatocellular carcinoma but not in various nonmalignant liver diseases. The association of p53 antibodies with malignancy was highly significant (p < 0.00003). In 73.8% (59 of 80) of the hepatocellular carcinoma sera the alpha-fetoprotein levels were elevated. Among the 21 alpha-fetoprotein-negative hepatocellular carcinoma sera, 5 were found to contain p53 antibodies (23.8%). In conclusion, an antibody response against p53 developed in a significant proportion of patients with hepatocellular carcinoma but not in those with nonmalignant liver diseases. Serological testing for p53 antibodies gives the opportunity to identify a subgroup of patients with hepatocellular carcinoma not detected by conventional tests for serum alpha-fetoprotein.
最近，p53基因畸变已被认为是肝癌发生的一个相关因素，在高风险和低风险地区的肿瘤中均如此。由于p53基因突变通常会导致肿瘤细胞中p53水平升高，这种细胞蛋白在肿瘤发展过程中可能会变得具有免疫原性。为了验证这一假设，我们分析了80名欧洲肝细胞癌患者血清中p53抗体的存在情况。为此，我们开发了一种以重组p53为抗原的免疫印迹分析方法。将来自不同急性和慢性肝病患者的67份血清用作对照。此外，还进行了血清甲胎蛋白检测。在肝细胞癌患者的血清中，25%（80份中的20份）发现了针对p53的循环抗体，而在各种非恶性肝病中未发现。p53抗体与恶性肿瘤的关联非常显著（p<0.00003）。在80份肝细胞癌血清中，73.8%（59份）的甲胎蛋白水平升高。在21份甲胎蛋白阴性的肝细胞癌血清中，有5份（23.8%）发现含有p53抗体。总之，相当一部分肝细胞癌患者会产生针对p53的抗体反应，而患有非恶性肝病的患者则不会。对p53抗体进行血清学检测，有机会识别出常规血清甲胎蛋白检测未发现的肝细胞癌患者亚组。
