ERCC1 protein, mRNA expression, and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma (HNSCC) patients treated with surgery and adjuvant cisplatin-based chemoradiation (CRT).

Abstract

5540 Background: Adjuvant cisplatin-based CRT improves overall survival (OS) in some HNSCC patients (pts) presenting with risk features, but toxicity is not negligible. ERCC1 is involved in NER pathway and is associated with resistance to chemo- and RT. We studied ERCC1 expression and the SNP T19007C in these pts. Methods: It is a retrospective study in HNSCC pts submitted to surgery and presenting with pathologic risk features. They were treated with 60-70 Gy and concurrent cisplatin 100 mg/m2d1, 22, 43. ERCC1 protein, mRNA expression and the SNP were studied in archived tissue blocks. ERCC1 expression was evaluated by immunohistochemistry, using a semi-quantitative H- score, and its mRNA expression was determined by quantitative RT-PCR. T19007C genotypes were detected using PCR-RFLP carried out in genomic DNA extracted from normal lymph nodes. Results: 69 pts (median age 56 y, 81% male) were studied. Primary sites: oral cavity 41%, larynx 32%, hypopharynx 16%, oropharynx 12%; stage IV 86%, pT3-pT4 78% and pN2-pN3 58%. 43 pts presented with ≥2 +ve lymph nodes, 27 with extracapsular spread and 18 with +ve margins. High-risk features were diagnosed in 40 pts (58%). During the median follow-up of 47 mo., we observed 30 deaths (22 disease-related). The 5-y OS was 40% and the 5-y disease-free survival was 31%. High H-score (>1.5) was seen in 32 pts (54%), who presented better 5-y OS (50% vs. 18%, HR 0.43, 95%CI 0.20-0.90, p=0.026). 15 out of 45 pts (33%), whose tumors had high ERCC1 mRNA expression (>3.1), presented better 5-y OS (86% vs. 30%, HR 0.26, 95%CI 0.14-1.01, p=0.052). Genotype distribution in 49 pts was 39% C/T, 37% C/C, and 24% T/T. No difference was detected among genotypes in terms of 5-y OS (45%, 46%, 46%; p=0.808). High H-score and ERCC1 mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Conclusions: High ERCC1 expression was associated with better prognosis in HNSCC pts submitted to adjuvant cisplatin-based CRT. It may be useful to better stratify these pts, however a prospective validation is needed. No significant financial relationships to disclose.