Analytical evaluation of a commercial in-house homologous recombination deficiency (HRD) assay for patients with epithelial ovarian cancers and its concordance with a reference standard.

Abstract

e17592 Background: Homologous recombination deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs) as approximately half of EOCs have molecular aberrations in homologous recombination repair (HRR) genes, including BRCA1/2 gene mutations. Poly ADP-ribose Polymerase inhibitors (PARPi) have reformed the management of BRCA1/2 mutant ovarian cancer patients and demonstrated activity also in tumor with HRD status. The evaluation of HRD together with BRCA1/2 gene alterations is nowadays critical to guide the therapy decision for all patients with EOC. Different methods to assessed HRD have been reported and different assays are being implemented in clinical practice. Here, we sought to evaluate the analytical validity of a commercial in house HRD assay as compared to a reference standard method. Methods: 59 consecutive case of EOCs were included in this study. DNA extracted from representative formalin-fixed paraffin-embedded (FFPE) tissue block of each case were subjected to next-generation sequencing (NGS) analysis of BRCA1/2 genes alterations and HRD status using the AmoyDx HRD Focus Panel (Amoy Diagnostics Ltd, Xiamen, Fujian, China). HRD status was assesses through AmoyDx Genomic Scar Score (GSS) considering the length, type and location of the genome-wide chromosomal copy number variation through SNP probes spread throughout the genome. Cases with a GSS > 50 were considered as HRD positive. For each case the same FFPE tissue block was sent to Myriad Genetic Laboratories for myChoice CDx testing as reference standard. Assay concordance was measured as positive (PPA), negative (NPA) and overall (OPA) percentage of agreement according to the different scores proposed by the manufacturers. Results: HRD status data were available for 52 (88.1%) and 56 (94.9%) samples considering in-house and reference standard assay, respectively, and 49 cases was available for concordance analyses. AmoyDx HRD Focus Panel identified 23/49 samples (46.9%) as HRD positive and 26 (53.1%) as HRD negative. The concordance of HRD status between AmoyDx HRD Focus Panel and myChoice CDx was 100% and 81,2% for positive (PPA) and negative (NPA) cases respectively, with an overall analytical concordance (OPA) of 87.8%. No discordance was seen in BRCA1/2 status between in-house and reference standard assay (OPA: 100%). Conclusions: The HRD status assessed by AmoyDx HRD Focus Panel is highly concordant with that obtained using the current standard reference method. Commercial in-house test may offer a cost-effective, reliable and robust alternative to the centralized assay for the evaluation of HRD status in patient with EOC.