TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck

Background and Purpose: TP53 gene-mutation and expression of p53 have been described to influence the radiosensitivity of tumour cells from head and n eck carcinomas. The present study was performed to evaluate whether TP53 mu tation may influence the clinical outcome of head and neck cancer patients treated with radiotherapy or surgery. Materials and methods: DNA was extracted from formalin-fixed paraffin-embed ded tissue sections from primary biopsies taken before radiotherapy. Gene m utations (in exons 5-9) were identified using denaturing gradient gel elect rophoresis (DGGE) as the initial scanning procedure and characterized by se quencing. Patients were treated with primary radiotherapy or surgery alone. Treatment was given according to the DAHANCA schedules with 5 or 6 weekly fractions (2 Gy) of radiotherapy (66-68 Gy). Most patients were also treate d with the hypoxic radiosensitizer Nimorazole. The results are reported as 5-year actuarial values, and differences estimated by log-rank analysis. Results: The present analysis is based on 114 patients with squamous cell c arcinoma of the larynx, pharynx and oral cavity diagnosed between March 199 2 and October 1996. Ninety patients received primary radiotherapy alone and 21 were treated with surgery. TP53 mutations were found in 45 patients (39 %) and in patients receiving radiotherapy, TP53 mutation was highly associa ted with poor prognosis. Loco-regional control rates (5-year actuarial valu es) for TP53 mutation was 29 vs. 54% for TP53 wildtype (P < 0.01). For dise ase-free survival the corresponding values were 13 and 38% (P < 0.01), resp ectively. The correlations were not found to be related to specific subtype s of mutations (e.g. missense mutations affecting DNA-contact or Zn-binding regions) but rather to the presence of any mutation at all. In contrast, T P53 mutation did not influence the response to surgery. Conclusions: A strong relationship was observed between TP53 mutation and p oor prognosis (increased risk of loco-regional failure and death) in head a nd neck cancer patients given primary radiotherapy but not surgery. (C) 200 1 Elsevier Science Ireland Ltd. All rights reserved.