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

Mei Kim Ang, Mihir R. Patel, Xiao Ying Yin, Sneha Sundaram, Karen Fritchie, Ni Zhao, Yufeng Liu, Alex J. Freemerman, Matthew D. Wilkerson, Vonn Walter, Mark C. Weissler, William W. Shockley, Marion E. Couch, Adam M. Zanation, Trevor Hackman, Bhishamjit S. Chera, Stephen L. Harris, C. Ryan Miller, Leigh B. Thorne, Michele C. HaywardWilliam K. Funkhouser, Andrew F. Olshan, Carol G. Shores, Liza Makowski, D. Neil Hayes

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)6542-6552
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number20
DOIs
StatePublished - Oct 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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