PO-236 Human ligase profiling to predict platinum sensitivity and clinical outcome in primary epithelial ovarian cancers

Abstract

IntroductionOvarian cancer (OC) is the third most common gynaecological cancer among women worldwide. In Europe, OC is the main cause of death among all the gynaecological tumours. DNA ligases play an essential role in maintaining genomic integrity by joining DNA breaks generated during replication and recombination. The human ligases, LIG I, LIG III and LIG IV are ATP-dependent DNA ligases. Our objective was to evaluate if ligases expressions could predict platinum sensitivity and clinical outcome in epithelial ovarian cancers.Material and methodsInvestigation of LIG I, LIG III and LIG IV expression in ovarian epithelial cancer was carried out in 525 consecutive ovarian epithelial cancer cases treated at Nottingham University Hospitals (NUH) between 1997 and 2010. Ligase expression was correlated to clinicopathological features, recurrence free survival (RFS) and ovarian cancer specific survival (OCSS).Results and discussionsHigh expression of LIG I was significantly associated with serous carcinoma (p<0.0001), higher FIGO stage at presentation (p<0.0001), higher tumour grade (p<0.0001), non-optimal surgical tumour de-bulking (p=0.004). High cytoplasmic ligase III expression was significantly associated with higher FIGO stage (p=0.002), higher histology grade (p=0.028), residual tumour following surgery (p=0.001), measurable disease before chemotherapy (p=0.006) and platinum resistance (p=0.025). High LIG IV expression was significantly associated with less residual tumour following surgical excision (p=0.006) and better response to platinum based chemotherapy (p=0.049). High LIG I and LIG III protein expressions were correlated with poor survival outcome. However, LIG IV was correlated with favourable outcome. LIG I expression was independently associated with poor outcome in cox multivariate model.ConclusionHuman Ligases are promising predictive biomarkers of platinum response and clinical outcome in epithelial ovarian cancer.