Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer

Neoadjuvant cisplatin-based chemotherapy has been widely used in the last d ecade for organ preservation or unresectable disease in advanced stage head and neck cancer. We examined the expression of a series of tumor markers t hat have been associated with chemotherapy resistance in pretreatment biops ies from 68 patients who received cisplatin-based neoadjuvant chemotherapy at either of two institutions. Patients received either cisplatin/5-fluorou racil (n = 49) or cisplatin/paclitaxel (n = 19), Expression of p53, glutath ione S-transferase pi (GST pi), thymidylate synthase (TS), c-erbB2, and mul tidrug resistance-associated protein was examined by immunohistochemistry. Expression of glutathione synthetase mRNA was measured by in situ hybridiza tion, The overall response rate for cisplatin-based neoadjuvant treatment w as 79%; The expression of several of the tumor markers was associated with resistance to neoadjuvant treatment, but none reached statistical significa nce. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 81% in the p53-negative group, whereas it was 30% in the p53-positive group for patients treated with neoadjuvant ch emotherapy (P < 0.0001). Expression of GST pi and TS was also significantly correlated with decreased OS after neoadjuvant treatment. At 3 years, the OS rate was 82% in the low GST pi score group, compared to 46% in the high GST pi score group (P = 0.0018). In the TS-negative group, the 3-year OS ra te was 71% compared with 40% in the TS-positive group (P = 0.0071). We conc lude that p53, GST pi, and TS may be clinically important predictors of sur vival in patients receiving neoadjuvant chemotherapy for head and neck canc er.