Homologous recombination deficiency (HRD) testing of high-grade serous carcinoma using cytological samples.

Abstract

Background: Homologous recombination deficiency (HRD) is associated with increased sensitivity to PARP inhibitor therapy in various cancer types, including high-grade serous carcinoma (HGSC). Current guidelines recommend HRD testing to guide treatment decisions in HGSG. The majority of HRD assays rely on tumour tissue analysis. The main objective of this study was to assess cytological HGSC samples for HRD testing.

Methods: Next generation sequencing using the Oncomine™ Comprehensive Assay Plus (OCAP) panel was performed on 110 matched cytological and histological samples from 55 treatment-naïve HGSC patients to determine the mutational status of 15 homologous recombination repair (HRR)-associated genes including BRCA1/2, and the HRD status based on BRCA1/2 mutational status and genomic instability metric (GIM). Concordance analysis was performed.

Results: Compared to matched histological samples, cytological HGSC samples revealed an overall concordance rate of 89.7% for HRR-associated gene mutations and of 100% for BRCA1/2 mutations, respectively. A moderate correlation between GIM values (Pearson correlation coefficient 0.48), but an overall concordance rate of 90.9% for the HRD status was observed.

Conclusions: Our findings demonstrate that cytological HGSC samples can be employed for HRR-associated gene mutation and HRD testing using next generation sequencing with the OCAP panel.