p53 protein is absent from the serum of patients with lung cancer.

p53 protein, which accumulates intracellularly in over half of all human tumours, has also been reported to be present in the sera of patients with various malignancies, including lung cancer. Using a quantitative immunoassay, we measured p53 protein concentrations in 216 sera from 114 lung cancer patients of whom 75 provided matched lung tumour tissues, which were also assayed for p53 protein. p53 protein levels above the detection limit of 0.04 ng ml-1 were detected in only two sera from lung cancer patients (0.14 ng ml-1 and 0.27 ng ml-1), but not in any of 13 sera from non-malignant lung disease patients or in 100 sera from normal non-diseased individuals. The presence of these apparent traces of serum p53 protein concentrations could not be related either to the p53 protein expression status of the primary lung tumours or to the tumour stage, grade or histological type. By pretreating these two sera with anti-p53 antibody linked to solid phase, and by the addition of mouse serum to neutralise possible heterophilic antibodies, the signals arising from these sera were shown to be non-specific and possibly caused by heterophilic antibodies. We conclude that our data do not support previous reports of p53 protein in the sera of lung cancer patients. Since immunoassays are subject to numerous sources of interference in serum, including heterophilic antibodies, we suggest that the results of p53 protein analysis of serum specimens should be interpreted with caution.