Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein.

Analyses of p53 antibodies in sera of patients with lung carcinoma define immunodominant regions in the p53 protein.
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肺癌患者血清中p53抗体的分析定义了p53蛋白中的免疫主导区域。

DOI:
10.1038/bjc.1994.159
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发表时间:
1994-05
影响因子:
8.8
通讯作者:
Soussi T
Soussi T
中科院分区:
医学1区
文献类型:
--
作者:
Schlichtholz B;Trédaniel J;Lubin R;Zalcman G;Hirsch A;Soussi T

文献摘要

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对肺癌患者血清中的人p53特异性抗体进行了分析。我们检测了24%(10/42)的肺癌患者血清中的p53抗体。分布如下:4/9个小细胞肺癌(SCLC),2/18个鳞状细胞肺癌(SCC),2/10个腺癌(ADC)和2/5个大细胞肺癌(LCC)。p53抗体在诊断时总是存在,在疾病进展期间不出现。使用原始的肽映射程序,我们精确地定位了p53抗体识别的p53表位。与抗体反应的免疫优势表位位于蛋白质的氨基和羧基末端,与乳腺癌患者或用p53免疫的动物中发现的表位相似。根据这些数据,我们认为p53抗体通过自身免疫过程发生,这是p53在肿瘤细胞中积累的结果。2例未检出恶性肿瘤的患者也检测到p53抗体。其中1例患者6个月后死于肺癌,提示p53抗体可能是p53改变的早熟标志物。
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.