Lubin R, Zalcman G, Bouchet L, Trédanel J, Legros Y, Cazals D, Hirsch A, Soussi T
Unité 301 INSERM, Institute de Génétique Moléculaire, Paris, France.
Nat Med. 1995 Jul;1(7):701-2. doi: 10.1038/nm0795-701.
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 and others 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%). 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.
p53改变是人类癌症中最常见的改变。它通常涉及错义突变，这些突变使p53蛋白稳定，进而积累，达到可通过免疫组织化学检测到的水平。我们和其他人已经证明，突变p53蛋白的这种过表达可在癌症患者中诱导特异性体液反应。通过各类癌症患者血清中p53抗体的存在来评估这一结果，而正常人群则不表现出此类抗体。在肺癌中，p53抗体的患病率很高（30%），且与该癌症中非常高的p53突变率（60 - 70%）相关。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不出现，这一观察结果因这些抗体大多为IgG（对应于二次免疫反应）而得到加强。这些结果表明体液反应是一个早期事件，并且p53抗体可在疾病临床表现之前用作p53改变的早熟标志物。
