ERCC-1 (E) expression and its effect on survival in patients (pts) receiving concurrent cisplatin (C) and radiation (R) for locally advanced head and neck cancer (HNC)

Abstract

e17033 Background: E is a DNA repair gene involved in the nucleotide excision repair pathway. Overexpression of E has been associated with resistance to C in patients with ovarian, gastric, and lung cancer. We retrospectively analyzed tissue from HNC pts who received concurrent C and R to determine if E expression was a significant independent predictor of survival. Methods: Eligible HNC pts had squamous cell histology and received definitive concurrent C and R at the Dallas VAMC. Tissue was immunostained for E using ERCC-1,clone 8F, 1:100 dilution (Abcam, Cat#ab2356, Cambridge, MA) diluted in ChemMate buffer (Ventana Medical Systems, Tucson, AZ) on a BenchMarkXT automated immunostainer using the UltraVIEW system with horseradish peroxidase and diaminobenzidine (DAB) chromogen (Ventana Medical Systems, Tucson, AZ) per the standard protocol of the UT Southwestern Pathology Immunohistochemistry Laboratory. E scoring was determined by 2 pathologists blinded to clinical outcomes. Scoring was as follows: 0 = 0% of tumor nuclei were positive, 1+ = less than 50%, 2+ = 50–75% and 3+ = 75–100%. Results: 73 consecutively treated patients were analyzed. Median age 59 (range 41 - 80); 99% male; 7% stage II, 19% stage III, 73% stage IV; primary site - 4% oral cavity, 56% oropharynx, 14% hypopharynx, 23% larynx, 3% nasopharynx; Tumor grade - 60% moderately differentiated, 4% well differentiated, 15% poorly differentiated, 21% not specified; Performance status 0–25%, 1–45%, 2–8%, unknown-22%; E scoring was 0 in 0%, 1+ (14%), 2+ (42%), 3+ (44%). In univariate analysis, E staining 3+ was not predictive of survival with a hazard ratio (HR) of .796 (95% CI .44–1.43; p = 0.44). In multivariate analysis, the only significant predictor was hypopharynx with a HR of 3.18 (95% CI 1.02–9.88; p = 0.046). HR for age > 60 was 2.16 (95% CI .96–4.86; p = 0.06). E staining 3+ was not predictive of survival with a HR of .69 (95% CI .3–1.56; p = 0.37). Median survival (MS) for the whole group was 2.8 years (y); 5y survival - 41%. MS for the E 3+ pts - 2.1y; 5y survival 38%. MS for the E < 3+ pts - 2.9y; 5y survival 44% (p = not significant). Conclusions: In our retrospective review of HNC patients receiving concurrent C and R, E staining was not a significant predictor of survival. No significant financial relationships to disclose.