Raedle J, Oremek G, Truschnowitsch M, Lorenz M, Roth W K, Caspary W F, Zeuzem S
Second Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
Eur J Cancer. 1998 Jul;34(8):1198-203. doi: 10.1016/s0959-8049(98)00056-2.
In hepatocellular carcinoma (HCC) of patients from the Western hemisphere, mutations in the p53 tumour suppressor gene are present in up to 37% of cases. Conformational change and cellular accumulation can initiate an immune response with generation of circulating autoantibodies to p53 protein. In the present study, we investigated 711 consecutive patients with chronic liver disease to evaluate the sensitivity and specificity of autoantibodies to p53 protein as a serological marker for HCC. Detection of p53 autoantibodies was performed using an enzyme-linked immunosorbent assay with immobilised recombinant p53 protein. Liver cirrhosis was present in 259 patients (36.4%) and a HCC was diagnosed in 75 patients (10.6%). Autoantibodies to p53 protein were detectable in 15 of 377 patients with chronic liver disease (4.0%) and in 10 of 259 patients presenting with liver cirrhosis (3.9%). All 25 p53 autoantibody-positive/HCC-negative patients were carefully investigated and no underlying malignancy was clinically detected, suggesting that elevated p53 antibody levels may not exclusively be detectable in patients with malignant disease. In patients with clinically manifest HCC, p53 autoantibodies were detected in 17 of 75 cases, thus resulting in a sensitivity of 22.7% and a specificity of 96.1%. In contrast, assessment of serum alpha-fetoprotein (AFP) resulted in a sensitivity and specificity of 69.3 and 91.8% (AFP > 20 ng/ml) and 53.3 and 99.1% (AFP > 100 ng/ml) for the detection of HCC, respectively. The data of the present study reveal that the presence of p53 autoantibodies in patients with chronic liver disease is not completely specific for HCC. Moreover, we obtained no direct evidence that p53 autoantibody formation precedes the clinical diagnosis of HCC. However, serological screening for HCC might be improved by combining AFP and p53 autoantibody assays.
在西半球患者的肝细胞癌（HCC）中，p53肿瘤抑制基因的突变在高达37%的病例中存在。构象变化和细胞蓄积可引发免疫反应，产生针对p53蛋白的循环自身抗体。在本研究中，我们调查了711例连续性慢性肝病患者，以评估针对p53蛋白的自身抗体作为HCC血清学标志物的敏感性和特异性。使用固定化重组p53蛋白的酶联免疫吸附测定法检测p53自身抗体。259例患者（36.4%）存在肝硬化，75例患者（10.6%）被诊断为HCC。377例慢性肝病患者中有15例（4.0%）可检测到针对p53蛋白的自身抗体，259例肝硬化患者中有10例（3.9%）可检测到。对所有25例p53自身抗体阳性/HCC阴性患者进行了仔细检查，临床上未检测到潜在恶性肿瘤，这表明p53抗体水平升高并非仅在恶性疾病患者中可检测到。在临床表现为HCC的患者中，75例中有17例检测到p53自身抗体，因此敏感性为22.7%，特异性为96.1%。相比之下，血清甲胎蛋白（AFP）检测HCC的敏感性和特异性分别为69.3%和91.8%（AFP>20 ng/ml）以及53.3%和99.1%（AFP>100 ng/ml）。本研究数据表明，慢性肝病患者中p53自身抗体的存在对HCC并非完全特异。此外，我们没有获得直接证据表明p53自身抗体的形成先于HCC的临床诊断。然而，联合AFP和p53自身抗体检测可能会改善HCC的血清学筛查。
