Abstract 338: Truncating TP53 mutations have prognostic significance in head and neck squamous cell carcinoma

Background: TP53 is a key gene in cellular homeostasis and is frequently mutated in head and neck squamous cell carcinoma (HNSCC). There is a variety of TP53 mutations, each with its own biological and clinical implication. Some HNSCC are TP53 wild type, amongst those caused by infection with the human papillomavirus (HPV). Aim of the study was to assess the prognostic significance of TP53 mutations in HNSCC and to identify the most relevant mutation. Methods: TP53 mutation status was assessed by direct sequencing in 141 consecutive HNSCC treated by surgery with radiotherapy when indicated and with a known HPV-status. The type of mutation was correlated with overall survival in a multivariate two-sided Cox regression analysis with wild type as reference. Results: HPV infections was found in 12 out of 141 cases (9%). Although a relation between HPV infection and a favorable prognosis was observed, the association was not significant. A TP53 mutation was found in 88 (62.4%) of the carcinomas and was not associated with survival. Tumors with a mutation resulting in a truncated protein (n=36, 25.5% consisting of nonsense, frame shift and splice site mutations), had a significantly worse overall survival (Hazard ratio: 2.54 with 95% confidence intervals of 1.28 and 5.05, p=0.008). Multivariate analysis showed that a truncating mutation is an independent risk factor, adjusted for HPV status. A missense (i.e. non-truncating) mutation did not influence prognosis. Other ways of mutation classification (disruptive vs. non-disruptive, hotspot vs. non-hotspot and DNA-binding vs. non-DNA-binding) were less discriminative and co-factors, including HPV-status were confounding in these associations. Conclusion: Truncating mutations in the TP53 gene are an important independent predictor for a poor prognosis of HNSCC patients. This patient group is an ideal target population for adjuvant therapy with chemoradiation or viral vector mediated TP53 gene transfer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 338. doi:10.1158/1538-7445.AM2011-338