Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy

6003 Background: Radiotherapy and most chemotherapeutic agents damage DNA and lack of adequate repair induces tumor cell death. Recently analysis of the nucleotide excision repair pathway identified ERCC1 as a predictor for platinating agents in multiple tumors. There are 6 DNA repair pathways which interrelate. We performed a more comprehensive analysis to identify clinically promising DNA repair biomarkers. Methods: 73 FFPE tumor samples from locally advanced HNC pts treated with carboplatin/taxane induction (I) followed by FHX-based chemoradiotherapy (CRT) were analyzed. IHC staining for 8 DNA repair biomarkers (5 pathways) was performed (ERCC1 (clone 8F1), XPF, pMK2, PARP, PAR1, pH2AX, MLH1, FANCD2), as well as relevant associated markers Ki67 (proliferation), EGFRvIII (truncated EGFR), p16 (HPV screen). IHC was analyzed by automated image processing, and 2 pathologists (blinded). Scores for nuclear/cytoplasmic intensity/quantity(IxQ) were correlated with response/survival. Immunoblot analysis in cell...