Ercc-1 Gene Expression As A Predictor Of Outcome Following Platinum-Based Chemotherapy In Epithelial Ovarian Cancer (Eoc)

5564 Background: The excision repair cross-complementation group 1 (ERCC1) enzyme is a crucial component of the nucleotide excision repair pathway which removes cisplatin-induced DNA adducts. High ERCC1 mRNA expression has been associated with platinum resistance in several tumor types. We assessed the relationship between ERCC1 expression and survival in EOC treated with platinum-based chemotherapy. Methods: The Edinburgh Ovarian Cancer Database contains prospectively collected clinical data for all EOC patients treated in SE Scotland. This was screened for patients treated with platinum-containing chemotherapy. 145 archival formalin-fixed, paraffin-embedded (FFPE) tumor samples were recovered and microdissected. mRNA was isolated and quantitative Real Time- PCR was performed for ERCC1. The maximal chi-squared method was used to determine optimal ERCC1 cut-points. Differences in survival between patients whose tumors expressed high/low ERCC1 levels were then compared by Kaplan-Meier analysis. Results: First-line chemotherapy consisted of single agent platinum (69%), platinum-taxane combinations (30%) or a platinum-topotecan combination (1%). Using an ERCC1 cut-point at the 80th percentile to define high expression was found to predict a significantly worse progression-free survival (PFS; p=0.005) and overall survival (p=0.040). In addition, for patients treated with carboplatin and paclitaxel, it was shown that high ERCC1 expression was associated with a worse PFS (p=0.018). Conclusions: ERCC1 gene expression predicts the outcome following platinum-based chemotherapy in EOC. Contrary to the findings of the only other study with >100 patients addressing this issue, the relationship holds for carboplatin and paclitaxel as well as for platinum alone. These findings go some way towards identifying a patient group that is less responsive to standard platinum-based chemotherapy. Alternative treatment strategies should be sought in these patients and tested in the setting of a randomised trial of biomarker guided versus standard therapy. The fact that gene expression analysis can be performed on FFPE tissue increases the applicability of this technology. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Response Genetics Inc, Response Genetics Ltd Response Genetics Inc, Response Genetics Ltd Response Genetics Inc