Zalcman G, Schlichtholz B, Trédaniel J, Urban T, Lubin R, Dubois I, Milleron B, Hirsch A, Soussi T
Service de Pneumologie, Hôpital Saint-Louis, Paris, France.
Clin Cancer Res. 1998 Jun;4(6):1359-66.
Alteration of the p53 gene is the most frequent genetic alteration in human cancer, and it leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasias have p53 antibodies in their sera. ELISA was used to detect anti-p53 antibodies in their sera of 167 patients with lung cancer. Among these, 32 individuals (16 positive for p53 antibodies and 16 negative) were monitored over a period of 30 months for p53 antibodies. Twelve of 16 antibody positive patients had reduced titers during chemotherapy that led to partial or complete remissions of disease. The specificity of these antibodies was confirmed by two different ELISA procedures and by immunoprecipitation. The very rapid, specific decrease in these antibodies during therapy suggests that a constant level of tumoral cells with nuclear accumulating p53 protein is necessary for a detectable humoral anti-p53 response. The good correlation found between the specific evolution of the p53 antibody titer and the response to therapy suggests that p53 antibodies could represent a useful tool for checking the response to therapy and for monitoring some relapses before they are clinically detectable.
p53基因改变是人类癌症中最常见的基因改变,它会导致突变型p53在肿瘤细胞核中积累。此外,已有研究表明,患有各种类型肿瘤的患者血清中存在p53抗体。采用酶联免疫吸附测定(ELISA)法检测167例肺癌患者血清中的抗p53抗体。其中,32例患者(16例p53抗体阳性,16例阴性)被监测p53抗体30个月。16例抗体阳性患者中有12例在化疗期间抗体滴度降低,化疗导致疾病部分或完全缓解。这些抗体的特异性通过两种不同的ELISA方法和免疫沉淀得到证实。治疗期间这些抗体非常迅速、特异性地降低,这表明具有核内积累p53蛋白的肿瘤细胞持续存在,对于可检测到的体液抗p53反应是必要的。p53抗体滴度的特异性变化与治疗反应之间的良好相关性表明,p53抗体可能是一种有用的工具,可用于检查治疗反应以及在临床可检测到复发之前监测某些复发情况。