Prognostic value of P53 and thymidylate synthase (TS) overexpression in patients with squamous cell carcinoma of the head and neck treated with neoadjuvant chemotherapy

Abstract

6081 Background: Neoadjuvant cisplatin-based chemotherapy has been widely used in the last decade for organ preservation or unresectable disease in advanced stage head and neck cancer. Thymidylate synthase (TS) and p53 are central molecules in the regulation of cell growth. Differences in the intracellular expression of these proteins by tumor cells may have predictive value for response to chemotherapy and early failure in patients with squamous cell cancer of the head and neck (SCCHN). We examined the expression of P53 and TS that have been associated with chemotherapy resistance. Methods: Immunohistochemistry was used to assess the tumor cell expression of TS and p53 in pre-therapy biopsies from 65 patients with SCCHN treated with induction chemotherapy. Results: The overall response rate for cisplatin-based neoadjuvant treatment was 80%. The expression of P53 and TS was associated with resistance to neoadjuvant treatment, but none reached statistical significance. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 80% in the p53-negative group, whereas it was 29% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P < 0.0001). Expression of TS was also significantly correlated with decreased OS after neoadjuvant treatment. In the TS-negative group, the 3-year OS rate was 69% compared with 38% in the TS-positive group (P = 0.0063). Conclusions: Our data showed that p53 and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer. No significant financial relationships to disclose.