Elevated expression of glutathione S-transferase pi and p53 confers poor prognosis in head and neck cancer patients treated with chemoradiotherapy but not radiotherapy alone

Abstract

Purpose: To examine the prognostic significance of expression of glutathione s-transferase pi (GST-pi) 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-pi 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-pi, 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-pi.

Figure 1.

RTOG 9003: Survival curves estimated by the Kaplan-Meier method. Patients with low expression of p53 and GST-π trend toward better survival when compared with patients with elevated expression of one or both markers (p=0.07).

Figure 2

RTOG 9501: Survival curves estimated by the Kaplan-Meier method. In this trial of adjuvant radiotherapy randomized with concomitant chemo-radiotherapy, patients with low expression of both markers had significantly improved survival compared with patients with elevated expression of one or both markers. (Panel 2A - All 142 patients p=0.02). In the combined chemotherapy arm (Panel 2B) expression of one or both markers correlated negatively with survival (p=0.06). Patients with high expression of both markers had a median survival of 1.5 years while for patients with low expression of both markers, median survival had not been reached. (p=0.006) . Analysis of the radiation alone cohort showed no significant difference in survival based on marker expression. (Panel 2C, p=0.54)

Figure 3.

Survival curves for black and white patients. Panel 3A - RTOG 9003. Panel 3B - RTOG 9501. For patients with available biopsy specimens for analysis, black patients had a significantly worse survival rate than did whites. In trial 9003, median survival was 2.2 years for white versus 1.5 years for blacks. Five year survival was 34% for whites and 22% for blacks. (p=0.011) In trial 9501, black patients had a strong trend for worse survival compared with whites. Median survival was 3.8 years for white versus 2.2 years for blacks. Five year survival was 46% for whites and 22% for blacks. (p=0.053).