Greenblatt M S, Feitelson M A, Zhu M, Bennett W P, Welsh J A, Jones R, Borkowski A, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 1997 Feb 1;57(3):426-32.
Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection. Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53. To determine whether p53 detection by IHC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample. Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers. The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg.
肿瘤抑制因子p53的失活似乎对与慢性乙型肝炎病毒感染相关的肝细胞癌（HCC）的发病机制很重要。尽管这种失活可能是由于p53基因的突变，但最近的证据表明，乙型肝炎病毒编码的X抗原（HBxAg）可与野生型p53结合并使其失活。因此，设计了实验来检验HBxAg阳性肝癌中p53突变频率较低这一假说。通过免疫组织化学（IHC）对16例中国患者的肝癌组织和非肿瘤肝脏组织中的HBxAg和p53进行检测，其中一半患者为乙型肝炎表面抗原携带者。通过免疫组织化学在所有患者的肿瘤和/或非肿瘤细胞中均可检测到HBxAg；其中6个样本也可检测到p53。为了确定通过免疫组织化学检测到的p53以及因此的稳定性是否与突变相关，对每个患者样本进行了p53第5至8外显子的测序。在16例HBxAg阳性病例中的13例（81%）中发现了野生型序列。因此，HBxAg是肝癌的常见标志物，与携带者和非携带者中野生型p53的持续存在相关。这些患者肝癌中p53突变的低频率意味着p53失活可能主要通过与HBxAg形成复合物而发生。
