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Elevated Expression of Glutathione S-Transferase and p53 Confers Poor Prognosis in Head and Neck Cancer Patients Treated with Chemoradiotherapy but not Radiotherapy Alone

Authors' Affiliation: University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland

Requests for reprints: Kevin J. Cullen, University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD 21201. Phone: 410-328-5506; Fax: 410-328-8455; E-mail: kcullen{at}umm.edu.

Purpose: To examine the prognostic significance of expression of glutathione s-transferase (GST-) and p53 in patients treated with radiation alone for locally advanced head and neck cancer [Radiation Therapy Oncology Group (RTOG), trial 9003] or radiation ± concomitant chemotherapy as postoperative adjuvant therapy (RTOG trial 9501).

Experimental Design: Immunohistochemical staining for p53 and GST- was done on tissue samples from 393 patients in RTOG 9003 and 142 patients in RTOG 9501. Kaplan-Meier survival analyses were done.

Results: Patients who had low expression of both markers had longer survival than patients who had high expression of both markers. In trial 9003, median survival was 2.4 years for patients with low expression of both markers versus 1.4 years for patients who had elevated expression of both markers (P = 0.07). These differences were highly significant in trial 9501 and were accounted for by the chemotherapy treated arm. In this group, patients with low expression of both markers had a median survival of 7.0 years compared with 1.4 years for patients with elevated expression of both markers (P = 0.006). In both trials, black patients had lower survival rates than did white patients and there was a trend toward higher expression of both markers in blacks compared with whites.

Conclusion: Given the poor outcome of chemoradiotherapy treatment patients with elevated expression of both p53 and GST-, these patients may not be appropriate candidates for chemoradiotherapy based on standard protocols. Some of the adverse outcome for black patients in both studies may be attributed to elevated expression of p53 and GST-.