Correlation of global expresssion of ERCC1 in head and neck squamous cell carcinoma with prognosis

Abstract

e17016 Background: The overexpression of excision repair cross-complementation group 1 (ERCC1), element of the Nucleotid Excision Repair (NER) pathway has been associated with resistance to platinum-based chemotherapy. We studied the correlation of ERCC1 immunohistochemical expression with overall survival and cancer-specific survival in patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) treated with cisplatin-based chemotherapy. Methods: Using a monoclonal antibody against ERCC1 (clone 8F1, Neomarker), we analyzed its immunohistochemical expression in pretherapeutic samples of 142 HNSCC patients treated in our center from 2000 to 2006. Forty-three patients were treated with surgery followed by adjuvant radiochemotherapy, 86 with concomitant radiochemotherapy with or without neoadjuvant chemotherapy and 13 with cisplatin-based chemotherapy for metastatic disease. Two independent observers blinded to clinical data evaluated ERCC1 expression using the H-score protocol (ranging from 0 to 3). Survival rates were estimated using the Kaplan-Meier method. Survival univariate analysis was performed using log-Rank test. Results: ERCC1was expressed intensively and diffusely in the nuclei 89% of the tumor samples had an H-score at least equal to 2. Treatment type and metastatic status were predictive of overall survival (respectively, p = 0.003 and p = 0.005). Higher expression of ERCC1 tended to be correlated with longer overall survival (p = 0.08). Conclusions: Our observations are at variance with recently published data about the predictive role of ERCC1 (Handra Luca CCR 2008). Overexpression of ERCC1 has also been associated with better outcome of operated NSCLC. Such differences may be due to inherent biological differences between study populations and certainly attributable to different roles of ERCC1 through oncogenesis.These controversial correlative results among studies and the intense and diffuse patterns of ERCC1 expression might also indicate a central role of ERCC1 in HNSCC oncogenesis and then provide a potential target. Further investigations about the role and predictive value of ERCC1 protein in anticancer treatments including cisplatin are warranted. No significant financial relationships to disclose.