Ovary: Oral Abstract: Clinico-pathological correlation of homologous recombination status in epithelial ovarian cancer: Surgeon's perspective
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
TCGA data using expensive multi-modality diagnostic platforms have shown that 50% epithelial ovarian cancers (EOCs) are estimated to be homologous recombination (HR) deficient (HRD). We developed a functional assay for HR using gamma H2AX-Rad51 immunofluoresence.
Primary cultures were developed in 50 consecutive EOCs from ascetic fluid and HR assay was performed.
50% patients were HRD based on the functional assay and show improved ex-vivo chemosensitivity to PARP inhibitor (PARPi) (PPV = 92%, NPV = 100%). HRD patients showed improved platinum sensitivity (53.8% vs 16.7%), survival (12 month OS - 41.7% vs. 11.5%) and optimal cytoreduction (80% vs. 62%) rates compared to HR competent (HRC) tumours which are less responsive and represent an unmet clinical need.
Personalised surgical and chemotherapeutic strategies may be developed for HR stratified EOCs. Primary surgery may be the preferred approach in HRC due to poor chemoresponse; surgical expertise/environment should be optimised to ensure optimal surgical outcome. Intra-operative hyperthermic treatment and selective HR inhibitors may improve subsequent chemoresponse in HRC and are currently being investigated.
Mukhopadhyay A, Plummer ER, Elattar A, Soohoo S, Uzir B, Quinn JE, et al. Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: Sensitivity to PARP inhibitors, platinum, and survival. Cancer Res. 2012;72:5675-82.