Expression of ERCC1, TUBB3, BRCA1, and TS as predictive markers of neoadjuvant chemotherapy for squamous cell carcinoma of the esophagus.

Abstract

47 Background: No predictive biomarker of the response to neoadjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil (NAC-DCF) is available for patients with squamous cell carcinoma of the esophagus (SCCE) in a clinical setting. The aim of this study was to identify the biomarkers associated with chemotherapeutic efficacy and long-term survival for patients with advanced SCCE who had received NAC-DCF followed by surgery. Methods: This study included 45 patients with advanced SCCE who received NAC-DCF between January 2008 and December 2012. The NAC-DCF was conducted as a phase II study (UMIN000007408). The expressions of excision repair cross-complementing-1 (ERCC1), class III beta-tubulin, breast cancer susceptibility gene I (BRCA1), and thymidylate synthase were investigated simultaneously in the pre-treatment endoscopic tumor biopsy samples. Results: The multivariate logistic regression analysis indicated that pathological responses were significantly associated with tumors with low ERCC1 expression (P = 0.016) and with tumors with high BRCA1 expression (P = 0.014). The incidence of pathological responses to DCF in patients with low ERCC1 and high BRCA1 expressions was 100%. The multivariate Cox proportional hazard model analysis for relapse-free survival (RFS) revealed tumors with high BRCA1 expression (P = 0.031, hazards ratio, 4.39) as independent prognostic factors. Conclusions: Low ERCC1 expression and high BRCA1 expression in patients with SCCE were predictive biomarkers for chemotherapeutic efficacy. High BRCA1 expression was considered as prognostic factors for long-term RFS. These results may be a helpful tool for tailoring chemotherapy of patients with SCCE. Prospective validation of this biomarker panel is warranted. Clinical trial information: UMIN000007408.