Schlichtholz B, Trédaniel J, Lubin R, Zalcman G, Hirsch A, Soussi T
Unité 301 INSERM, Institut de Génétique Moléculaire, Paris, France.
Br J Cancer. 1994 May;69(5):809-16. doi: 10.1038/bjc.1994.159.
Antibodies specific for human p53 were analysed in sera of lung cancer patients. We detected p53 antibodies in the sera of 24% (10/42) of patients with lung carcinoma. The distribution was as follows: 4/9 small-cell lung carcinomas (SCLCs), 2/18 squamous cell lung carcinomas (SCCs), 2/10 adenocarcinomas (ADCs) and 2/5 large-cell lung carcinomas (LCCs). p53 antibodies were always present at the time of diagnosis and did not appear during progression of the disease. Using an original peptide-mapping procedure, we precisely localised the p53 epitopes recognised by p53 antibodies. Immunodominant epitopes reacting with antibodies were localised in the amino and carboxy termini of the protein, similar to those found in breast carcinoma patients or in animals immunised with p53. In light of these data, we suggest that p53 antibodies occur via a self-immunisation process that is the consequence of p53 accumulation in tumour cells. p53 antibodies were also detected in two patients without detected malignant disease. One of these patients died 6 months later of lung carcinoma, suggesting that p53 antibodies may be a precocious marker of p53 alteration.
对肺癌患者血清中针对人p53的特异性抗体进行了分析。我们在24%(10/42)的肺癌患者血清中检测到了p53抗体。分布情况如下:4/9例小细胞肺癌(SCLC)、2/18例肺鳞状细胞癌(SCC)、2/10例腺癌(ADC)和2/5例大细胞肺癌(LCC)。p53抗体在诊断时始终存在,在疾病进展过程中未出现。使用一种原始的肽图谱分析方法,我们精确地定位了p53抗体识别的p53表位。与抗体反应的免疫显性表位位于该蛋白的氨基和羧基末端,类似于在乳腺癌患者或用p53免疫的动物中发现的表位。根据这些数据,我们认为p53抗体是通过自身免疫过程产生的,这是p53在肿瘤细胞中积累的结果。在两名未检测到恶性疾病的患者中也检测到了p53抗体。其中一名患者6个月后死于肺癌,这表明p53抗体可能是p53改变的早熟标志物。