Serum anti-p53 in relation to mutations across the entire translated p53 gene in colorectal carcinomas

Previous reports have claimed that antibodies to mutated p53 protein indica te poor outcome in malignant disease. The mechanism behind this highly spec ific process is unclear, although it has been claimed that certain DNA alte rations are prone to induction of immune response, since wild-type p53 is a lmost never immunogenic. The aim of the present analysis was to evaluate wh ether the presence of anti-p53 was statistically significantly related to a ny certain DNA alterations in the entirely expressed p53 gene in primary tu mors of colorectal cancer. P53 serum antibodies were determined by an enzym e linked immunosorbant assay (ELISA). P53 antibodies were detected in serum of 24 of 88 patients (27%). Twenty-two of 24 (92%) sero-positive patients had mutations in their p53 gene while only 22 of 64 (34%) sero-negative pat ients had p53 mutations (p<0.01). Mutations were mainly missense with a tre nd to significantly higher frequency of deletions in sero-negative patients compared to sero-positive subjects (8/25, 32% and 2/22, 9% respectively, p <0.08). Mutations in sero-positive patients were mainly located in exon 5 a nd 7 and within conserved regions (17 of 22 mutations). In sero-negative pa tients missense mutations were usually located in exon 5, 7 and 8 being als o most frequently located within conserved regions. Most of the p53 deletio ns in sero-negative patients were however located outside conserved regions (seven of eight deletions). There was no statistical difference between se ro-positive and negative patients concerning the spectrum of mutations alon g the expressed gene. Our study demonstrates that p53 antibodies are usuall y related to p53 gene mutations but a mutational event is not sufficient to elicit self-immunization. Cellular protein binding to p53 or individual di fferences of major histocompatibility complex based presentation of p53 pro tein sequences by immune cells is therefore the most likely explanation bet ween sero-negative and sero-positive patients.