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DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

  • Author(s): Seiwert, Tanguy Y
  • Wang, XiaoZhe
  • Heitmann, Jana
  • Villegas-Bergazzi, Vivian
  • Sprott, Kam
  • Finn, Stephen
  • O'Regan, Esther
  • Farrow, Allan D
  • Weichselbaum, Ralph R
  • Lingen, Mark W
  • Cohen, Ezra EW
  • Stenson, Kerstin
  • Weaver, David T
  • Vokes, Everett E
  • et al.
Abstract

Background

Induction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.

Methods

Expression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.

Results

We found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.

Conclusions

We identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated.

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