p53 and bcl-2 expression in locally advanced squamous cell head-neck cancer treated with platinum based chemotherapy and radiotherapy

Background: The role of apoptosis regulating oncoproteins in defining respo nse to cytotoxic therapy remains poorly understood. Loss of wild type p53 f unction and bcl-2 protein overexpression are well known to inhibit the apop totic pathway in in vitro studies. Methods: We immunohistochemically examin ed the nuclear accumulation of mutant p53 and the cytoplasmic overpression of bcl-2 proteins in 76 patients with locally advanced inoperable squamous cell cancer of the head and neck area. Patients were reated with platinum b ased cheomtherapy and radiotherapy (37 with induction and 39 with concurren t chemotherapy). The median follow up period was 72 months. Results: Thirty -five (46%) cases were positive for p53 and 41 (54%) negative, whilst 19 (2 5%) and 57 (75%) cases were positive and negative for bcl-2 repsectively. A high percentage of bcl-2 positive cells was associated with a low incidenc e of nodal involvement. A statistically significant higher percentage of p5 3 postive cells was observed in the group of patients with complete disappe arance of the disease as compared to the group with residual disease after treatment (p = 0.01). High percentage of p53 positive cells and concurrent chemoradiotherapy was associated with better local progression free surviva l (p = 0.05 and 0.02). In multivariate analysis, the type of prognostic var iable for local relapse (p = 0.02) and overall survival (p = 0.03). Conclus ion: The present study provides evidence that p53 nuclear accumulation may be associated with better response to DNA damaging cytotoxic agents. The as sociation of wild type p53 loss with decreased DNA repair enzyme activity i s a possible explanation. Induction platinum based chemotherapy may contrib ute to the selection of clonogenic cells with a radioresistant phenotype.