SERUM P53 ANTIBODIES AS EARLY MARKERS OF LUNG-CANCER

SERUM P53 ANTIBODIES AS EARLY MARKERS OF LUNG-CANCER
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DOI:
10.1038/nm0795-701
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发表时间:
1995-07-01
期刊:
影响因子:
82.9
通讯作者:
SOUSSI, T
SOUSSI, T
中科院分区:
医学1区
文献类型:
--
作者:
LUBIN, R;ZALCMAN, G;SOUSSI, T

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p53突变是人类癌症中最常见的突变。它通常涉及稳定p53蛋白的错义突变,p53蛋白反过来积累,达到免疫组织化学检测到的水平。我们(1-4)和其他人(5-8)已经证明,p53突变蛋白的过表达可以在癌症患者中诱导特异性的体液反应。这一结果是通过各种类型癌症患者血清中p53抗体的存在来评估的,而正常人群不表现出这种抗体。在肺癌中,p53抗体的患病率很高(30%),并且与这种癌症中非常高的p53突变率(60-70%)相关(2,8)。我们发现这些抗体在诊断时总是存在,但在肿瘤发展过程中从未出现,这些抗体主要是IgG,对应于二次免疫反应,这一事实加强了这一观察。这些结果表明,体液反应是一个早期事件,p53抗体可以作为临床表现前p53改变的早熟标志物。
The p53 alteration is the most common alteration found in human cancer. It usually involves missense mutations that stabilize the p53 protein, which in turn accumulates, reaching levels detectable by immunohistochemistry. We(1-4) and others(5-8) have demonstrated that this overexpression of mutant p53 protein can induce a specific humoral response in cancer patients. This result was assessed by the presence of p53 antibodies in sera of patients with various types of cancers, whereas normal populations do not exhibit such antibodies. In lung cancer, the prevalence of p53 antibodies is high (30%) and is correlated with a very high rate of p53 mutations in this cancer (60-70%)(2,8). We show that these antibodies are always present at the time of diagnosis, but never appear during tumour development, an observation strengthened by the fact that these antibodies are mostly IgG, corresponding to a secondary immune response. These results suggest that the humoral response is an early event and that p53 antibodies can be used as a precocious marker of p53 alteration before clinical manifestation of the disease.