C Hofele1, M Schwager-Schmitt, M Volkmann. 1. Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie der Universität Heidelberg, Germany. chofele@med.uni-heidelberg.de
Abstract
BACKGROUND: p53 gene aberrations are the most common genetic changes seen in human carcinogenesis. Frequently, single point mutations are detected, resulting in increased levels of (an aberrant) p53 protein in tumor cells. The cellular protein produced appears to become immunogenic during tumor development, inducing the production of circulating antibodies against p53. METHODS: For this study, sera from 126 patients with oral squamous cell carcinomas (102 primary tumours and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and their further clinical course was followed up for more than 5 years. 80 sera from internal medicine patients without known or suspected neoplasm served as control. A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova, Hamburg was used to detect p53 autoantibodies. RESULTS: In 18.6 % of the patients with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and also in 50 % of the patients with recurrent or local secondary carcinomas. None of the sera of the control group was positive. Patients with anti-p53 have noticeably poorer prognosis (Log Rank Test, p < 0.005). After a period of 5 years, the overall survival rate of the p53-positive group was 24 % - less than half of that of the p53-negative group with a survival rate of 51 %. CONCLUSIONS: : The detection of p53 autoantibodies definitely permits a clearer prognostic assessment, which in turn influences clinical procedures. If p53 autoantibodies are detected in a patient during therapy, the applied therapeutic method should be reconsidered and the patient be more closely observed than other, p53 negative patients.
BACKGROUND:p53 gene aberrations are the most common genetic changes seen in humancarcinogenesis. Frequently, single point mutations are detected, resulting in increased levels of (an aberrant) p53 protein in tumor cells. The cellular protein produced appears to become immunogenic during tumor development, inducing the production of circulating antibodies against p53. METHODS: For this study, sera from 126 patients with oral squamous cell carcinomas (102 primary tumours and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and their further clinical course was followed up for more than 5 years. 80 sera from internal medicine patients without known or suspected neoplasm served as control. A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova, Hamburg was used to detect p53 autoantibodies. RESULTS: In 18.6 % of the patients with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and also in 50 % of the patients with recurrent or local secondary carcinomas. None of the sera of the control group was positive. Patients with anti-p53 have noticeably poorer prognosis (Log Rank Test, p < 0.005). After a period of 5 years, the overall survival rate of the p53-positive group was 24 % - less than half of that of the p53-negative group with a survival rate of 51 %. CONCLUSIONS: : The detection of p53 autoantibodies definitely permits a clearer prognostic assessment, which in turn influences clinical procedures. If p53 autoantibodies are detected in a patient during therapy, the applied therapeutic method should be reconsidered and the patient be more closely observed than other, p53 negative patients.
Authors: Michael Bergqvist; Daniel Brattström; Kristina Lamberg; Patrik Hesselius; Johan Wernlund; Anders Larsson; Gunnar Wagenius Journal: Neoplasia Date: 2003 Jul-Aug Impact factor: 5.715