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.
Summary 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.
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