A comprehensive evaluation of the prognostic value of ERCC1 protein expression, mRNA and genotype in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN)

Abstract

6011 Background: ERCC1 has been associated with resistance to cisplatin (CDDP). In this retrospective study we analyzed ERCC1 protein expression, mRNA levels and single nucleotide polymorphisms (SNP) at codon 118 and examined each as a potential predictive/prognostic marker in LA-SCCHN pts treated with concurrent CDDP and radiation (CCRT). Methods: Records of 91 consecutive LA-SCCHN pts treated at the Tom Baker Cancer Centre between Aug 2000 and Mar 2005 were reviewed. ERCC1 was evaluated from pre-treatment formalin-fixed paraffin-embedded (FFPE) biopsies. Protein expression was assessed by conventional immunohistochemistry (IHC) using a 4-point semiquantitative scale as well as by immunofluorescence combined with automated quantitative analysis (AQUA). Quantitative RT-PCR and a pre-made TAQMAN genotyping assay were used to evaluate mRNA levels and the codon 118 SNP respectively. Results: FFPE biopsies were available from 57 pts (63%). Patient characteristics were as follows: mean age 56.4 years (range 43–75), 82.5% male, 77.2% KPS > 80%, 50.9% oropharyngeal primaries. ERCC1 protein expression was high in 39 pts (72%) by IHC versus 17 pts (31%) using AQUA. Ten pts (26%) had high levels of mRNA. C/C, C/T and T/T genotype frequencies were 17%, 43%, and 40%, respectively. ERCC1 IHC grading was significantly Spearman correlated (r=0.47) with AQUA scores. mRNA and protein expression were not correlated. The complete response rate was 89.3%. With a median follow-up of 44 months (range 3, 85), the 5 year overall survival (OS) was 68.2%. ERCC1 levels did not predict response, regardless if the pts received 100% versus <100% of CDDP. A nonsignificant increase in locoregional recurrence (LRR), recurrence at any site (ALLREC) and worse OS was observed with high IHC score. The C/C and C/T genotype was also predictive of LRR (HR=7.4, 95%CI: 0.9–58.6, p=0.06), ALLREC (HR=8.6, 95%CI: 1.1–67.2, p=0.04), and higher mortality (HR=3.9, 95%CI: 0.8–17.8, p=0.08). mRNA levels did not predict outcome. Conclusions: Our preliminary results suggest that high ERCC1 protein expression as well as the C/C or C/T genotype may be potential prognostic markers for LA-SCCHN pts treated with CCRT. No significant financial relationships to disclose.