Titration of serum p53 antibodies in 1,085 patients with various types of malignant tumors: a multiinstitutional analysis by the Japan p53 Antibody Research Group

Abstract

Background: There have been very few large-scale, multiinstitutional studies of surveillance of serum p53 antibodies (S-p53 Abs) in patients with various malignant tumors.

Methods: A highly specific, quantitative enzyme-linked immunosorbent assay (ELISA) kit was developed and used to evaluate the efficiency of detecting p53 Abs. A cut-off value was established by analyzing sera from 205 healthy volunteers as reference individuals. Sera from 1085 patients with various types of primary malignant tumors were studied for the presence of S-p53 Abs before treatment. Sera from 34 patients were selected randomly for a competition assay to ensure that antibodies were specific to p53 protein. Carcinoembryonic antigen (CEA) was assessed to compare its positive rate with the positive rate of S-p53 Abs.

Results: The median value of S-p53 Abs in healthy control individuals was 0.33 U/mL (range, 0.0-4.39 U/mL). Based on reference values that were calculated using parametric determination of the lower 0.95 fraction of the reference distribution in healthy control individuals, the cut-off value was determined as 1.3 U/mL. Two hundred twenty-one of 1085 patients (20.4%) were positive for S-p53 Abs. The highest relevance of S-53 Abs was associated with head and neck carcinoma (32%), followed by esophageal carcinoma (30%), colorectal carcinoma (24%), and carcinoma of the uterus (23%). The positive rate for S-p53 Abs was higher compared with the positive rate for CEA in patients with squamous cell carcinoma.

Conclusions: Surveillance of S-p53 Abs is useful in detecting various types of malignant tumors, particular in patients with squamous cell carcinoma.