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Prognostic Value of p53, Glutathione S-Transferase , and Thymidylate Synthase for Neoadjuvant Cisplatin-based Chemotherapy in Head and Neck Cancer¹

Lombardi Cancer Center, Georgetown University, Washington, D.C. 20007 [H. S., A. A. R., B. T., M. La., A. B., M. Le., K. J. C.]; Johns Hopkins Oncology Center, Baltimore, Maryland 21205 [E. I. H., A. A. F.]; Queens University, Belfast, United Kingdom BT9 7AB [P. G. J.]; and Department of Otolaryngology, Kanazawa University, Kanazawa, Ishikawa 920, Japan [H. S.]

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. We examined the expression of a series of tumor markers that have been associated with chemotherapy resistance in pretreatment biopsies from 68 patients who received cisplatin-based neoadjuvant chemotherapy at either of two institutions. Patients received either cisplatin/5-fluorouracil (n = 49) or cisplatin/paclitaxel (n = 19). Expression of p53, glutathione S-transferase (GST), thymidylate synthase (TS), c-erbB2, and multidrug resistance-associated protein was examined by immunohistochemistry. Expression of glutathione synthetase mRNA was measured by in situ hybridization. The overall response rate for cisplatin-based neoadjuvant treatment was 79%. The expression of several of the tumor markers 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 81% in the p53-negative group, whereas it was 30% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P < 0.0001). Expression of GST and TS was also significantly correlated with decreased OS after neoadjuvant treatment. At 3 years, the OS rate was 82% in the low GST score group, compared to 46% in the high GST score group (P = 0.0018). In the TS-negative group, the 3-year OS rate was 71% compared with 40% in the TS-positive group (P = 0.0071). We conclude that p53, GST, and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer.

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