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56P - Clinicopathological, predictive and prognostic significance of XRCC1-Ligase III heterodimer expression in ovarian cancer

Presentation Number
56P
Lecture Time
17:10 - 17:10
Speakers
  • M L. Alabdullah (Birmingham, GB)
Session Name
Location
Foyer La Scene, Paris Marriott Rive Gauche, Paris, France
Date
05.03.2018
Time
17:10 - 18:00
Authors
  • M L. Alabdullah (Birmingham, GB)
  • Paul Moseley (Nottingham, GB)
  • Steve Chan (Nottingham, GB)
  • Emad Rakha (Nottingham, GB)
  • S Madhusudan (Nottingham, GB)

Abstract

Background

Ovarian cancer is the leading cause of death from gynaecologic malignancy. The platinum-based chemotherapy remains the standard initial treatment for ovarian cancer patients. Platinum resistance and recurrence is a formidable problem that impacts clinical outcomes in ovarian cancer patients. XRCC1-Ligase III heterodimer is a key player in DNA base excision repair (BER), single strand break repair (SSBR) and alternative non-homologous end joining (alt-NHEJ) pathway for double strand breaks (DSBs) Our objective was to evaluate if XRCC1-ligase III expressions could predict platinum and clinical outcome in epithelial ovarian cancers.

Methods

Investigation of the expression of XRCC1 and Ligase III in ovarian epithelial cancer was carried out on tissue microarrays of 525 consecutive ovarian epithelial cancer cases treated at Nottingham University Hospitals (NUH) between 1997 and 2010 and their expression was correlated to clinicopathological outcomes as well as to recurrence free survival (RFS) and ovarian cancer specific survival (OCSS).

Results

High nuclear XRCC1 expression was significantly associated with serous cystadenocarcinomas (p = 0.0000), higher FIGO stage at presentation (p = 0.001), residual tumour following surgery (p = 0.038), measurable disease before chemotherapy (p = 0.002) and platinum resistance (p = 0.002). 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 nuclear staining was significantly associated with serous cystadenocarcinomas (p = 0.017). High XRCC1 was significantly positively highly correlated with high nuclear LIG3 (p < 0.0000). High XRCC1 and LIG III protein expressions were correlated with poor outcome.

Conclusions

XRCC1-Ligase III heterodimer is a promising predictive biomarker of platinum response in epithelial ovarian cancer.

Legal entity responsible for the study

This work has been approved by Nottingham Biobank Committee

Funding

Has not received any funding

Disclosure

All authors have declared no conflicts of interest.

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