Abstract 2804: ERCC1 (excision repair cross complementing group 1) is a predictive biomarker of survival in squamous cell carcinoma of the head and neck (SCCHN)

Abstract

Abstract Introduction: We analyzed SCCHN archival tissue in order to determine if baseline ERCC1 levels as measured by AQUA is associated with prognosis, benefit from adjuvant treatment or T stage in patients with resectable SCCHN. Experimental Procedures: Tissue microarrays containing head and neck squamous cell carcinoma samples obtained from patients treated at Fox Chase Cancer Center from 1990-2002 were constructed. Slides were stained by a modified indirect immunofluorescence method. Sections were incubated with ERCC1 antibody (8F1, Lab Vision) and wide-spectrum screening rabbit cytokeratin antibody (Dako Z0622). Prolong Gold mounting medium (P36931; Molecular Probes) containing 4,6-Diamidino-2-phenylindole (DAPI) was used to define tissue nuclei. A binary image (tumor mask) was created from the cytokeratin image of each histospot. ERCC1 levels were measured using fluorescent immunohistochemistry on the HistoRx PM-2000 image analysis platform and the data analyzed using AQUA algorithms. The in situ biomarker profiling system generated quantitative measurements of patient protein levels based on AQUA scores derived from fluorescent output of labeled markers. Tumor mask, nuclear, and cytoplasmic ERCC1 expression were measured. Baseline demographic and prognostic information was compared using Student's t-test for continuous variable or Fisher's exact tests for categorical variable. Analysis for overall survival was performed using Kaplan-Meier method, with comparisons using the log-rank test. Cox proportional hazard models were also used to examine the effect of ERCC1 after adjusted for the pathological T stage. Results: Tissue was analyzed from 109 patients (70 male, 39 females). Primary sites included tongue (34), glottic (15), retromolar trigone (10), tonsil (5), pyriform sinus (3), oral cavity (36), other (6). 33 were treated with surgery. 76 received adjuvant radiation or platinum based chemoradiation. The ERCC1 expression by AQUA score was defined as high versus low at the 30th percentile (262.37 in nuclear compartment, 161.31 in cytoplasmic compartment, 361.09 in tumor mask). In the 33 patients treated with surgery alone, there was no association with ERCC1 status and survival. In this group, low ERCC1 levels in all 3 compartments was associated with a higher T stage and tumor size (p=0.05 in nuclear, p=0.003 in tumor mask, p=0.05 in cytoplasm). Among the 76 patients who received adjuvant radiation/chemoradiation, low ERCC1 measured in the nuclear compartment was associated an increased survival (p=0.02). Conclusions: Low nuclear ERCC1 expression as defined by AQUA score in SCCHN is associated with greater T stage and benefit to adjuvant therapy with radiation/chemoradiation. We are developing a study to guide treatment selection for recurrent/metastatic disease based on ERCC1 status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2804.