P53 ANTIBODIES IN PATIENTS WITH VARIOUS TYPES OF CANCER - ASSAY, IDENTIFICATION, AND CHARACTERIZATION

Alteration of the p53 gene is the most frequent genetic alteration in human cancer and leads to the accumulation of mutant p53 in the nucleu s of tumor cells, In addition, it has been shown that patients with va rious types of neoplasia have p53 antibodies in their sera which could be used as an indirect diagnostic procedure for p53 alteration. Using a new ELISA, we have analyzed the sera from more than 1000 patients w ith various types of cancer and from healthy blood donors, We demonstr ate that p53 antibodies are detected mainly in cancer patients and are strictly proportional to the occurrence of p53 mutations. Using vario us immunological approaches, these antibodies were unambiguously demon strated to be directed toward the human p53 protein, Isotyping analysi s of these antibodies strongly suggested that they correspond to a hum oral response to the p53 protein which accumulates in the tumor cell, This finding suggests that serological analysis, combined with histoch emistry, is suitable for assessing the integrity of the p53 gene in ca ncer patients.