Abstract
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.
Highlights
Wild-type p53 protein is a nuclear transcription factor with multiple functions, including the induction of a GI/S cell cycle checkpoint, DNA repair and programmed cell death, following genomic damage (Kuerbitz et al, 1992; Lowe et al, 1993; Smith et al, 1994)
Missense mutation in most cases leads to the expression of a conformationally altered, non-functional mutant p53 protein which accumulates in the nucleus of affected cells and can be demonstrated by immunochemical techniques
In addition to immunohistochemistry, which has been extensively used in clinical studies, enzyme-linked immunosorbent assay (ELISA) methods have been developed to detect both mutant and wild-type p53 protein overexpression in tumour tissues (Midgley et al, 1992; Vojtesek et al, 1992; Hassapoglidou et al, 1993)
Summary
Wild-type p53 protein is a nuclear transcription factor with multiple functions, including the induction of a GI/S cell cycle checkpoint, DNA repair and programmed cell death, following genomic damage (Kuerbitz et al, 1992; Lowe et al, 1993; Smith et al, 1994). P53 mutation (Miller et al, 1992; Gazzeri et al, 1994; Ryberg et al, 1994) and protein accumulation (Caamano et al, 1991; Brambilla et al, 1993) frequently occur in primary lung carcinoma, which is the leading cause of cancer mortality in North America (Boring et al, 1993) Prognosis for these patients is largely dependent on the stage of the tumour presenting at clinical diagnosis, other factors, including p53 overexpression in tumour tissue, have been reported to predict reduced patient survival (Quinlan et al, 1992; Mitsudomi et al, 1993a). This study, comparing p53 protein concentrations in sera and tumour tissue extracts of patients with primary lung cancer, as well as reporting the measurements of p53 protein levels in sera from nonmalignant lung disease patients and from normal individuals, suggests that p53 protein is not present in the sera of patients with lung cancer
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