The immune response against p53 in patients with squamous cell carcinoma of the upper aerodigestive tract is unrelated to mutations in hot spot regions

Objective: Mutations of the p53 gene are the most prevalent genomic changes in human malignancies. The detection of these mutations is usually carried out by gene sequencing or with immunohistochemical methods. A new approach is to search for p53 antibodies in serum of cancer patients. The cause for the production of antibodies against p53 is unclear. The aim of this study was to show the correlation between p53 pointmutations and p53 antibodies in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods: A semiquantitative ELISA was employed to screen the serum of 117 patients with SCCHN for p53 antibodies, Sixty-one tumor samples were evaluated with SSCP-analysis for point mutations in exons 4 to 9. Results: Twenty-three (19.7%) of the cancer patients had antibodies to p53. There was no significant difference in the frequency of p53 point mutations in exon 4 to 9 between the whole cancer patient group and the p53 antibody positive group. Conclusions: The accumulation of p53 in the tumor cell is one hypothesis as to how p53 becomes immunogenic. This leads to a decrease in tolerance after a certain amount of time. In contrast to this it is assumed that after a p53 point mutation, important protein determinants are changed and p53 becomes antigenic. The results of this study indicate that p53 point mutations in SCCHN seem to have no influence on the development of p53 antibodies, Therefore this study supports the theory that the loss of tolerance and subsequently the antibody production is induced by an accumulation of p53, The type of p53 point mutations on exon 4-9 seems to have no influence that p53 gains immunogenic potential in SCCHN.