High XRCC1 protein expression is associated with poorer survival in patients with head and neck squamous cell carcinoma

Abstract

Purpose: We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome.

Experimental design: XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1).

Results: Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44-8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16(INK4a)-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52-4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06-0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36-15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08-0.92, respectively; P = 0.037).

Conclusions: In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment.

Figure 1

A, representative examples of XRCC1 immunostaining in head and neck squamous cell carcinoma at different staining intensities. i, intensity 0; ii, intensity 1+; iii, intensity 2+; and iv, intensity 3+. Magnification 200×. B, distribution of XRCC1 Allred score (range 0–8) in the overall study population.

Figure 2

Kaplan–Meier estimates of the probability of overall survival (A–C) and PFS (D–F) according to XRCC1 expression in whole cohort (A, D), CRT cohort (B, E), and non-CRT cohort (C, F).

Figure 3

Kaplan–Meier estimates of the probability of overall survival in patients who are (i) p16^INK4a positive, XRCC1 low; (ii) p16^INK4a positive, XRCC1 high; (iii) p16^INK4a negative, XRCC1 low; and (iv) p16^INK4a-negative, XRCC1-high.