ANALYSES OF P53 ANTIBODIES IN SERA OF PATIENTS WITH LUNG-CARCINOMA DEFINE IMMUNODOMINANT REGIONS IN THE P53 PROTEIN

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 pa tients with lung carcinoma. The distribution was as follows: 4/9 small -cell lung carcinomas (SCLCs), 2/18 squamous cell lung carcinomas (SCC s), 2/10 adenocarcinomas (ADCs) and 2/5 large-cell lung carcinomas (LC Cs). p53 antibodies were always present at the time of diagnosis and d id not appear during progression of the disease. Using an original pep tide-mapping procedure, we precisely localised the p53 epitopes recogn ised by p53 antibodies. Immunodominant epitopes reacting with antibodi es were localised in the amino and carboxy termini of the protein, sim ilar to those found in breast carcinoma patients or in animals immunis ed with p53. In light of these data, we suggest that p53 antibodies oc cur via a self-immunisation process that is the consequence of p53 acc umulation in tumour cells. p53 antibodies were also detected in two pa tients without detected malignant disease. One of these patients died 6 months later of lung carcinoma, suggesting that p53 antibodies may b e a precocious marker of p53 alteration.