Homologous recombination deficiency testing in ovarian cancer: the diagnostic experience of a referral Italian institution.

Abstract

Aims: Recently, precision medicine has drastically modified clinical paradigm for the clinical stratification of high-grade serous ovarian cancer (HGSOC) patients. International societies approved poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) to treat platinum-sensitive BRCA1/2 defective HGSOC patients. Beyond BRCA1/2, functional defects in homologous recombination repair (HRR) proteins laid the basis for genomic instability evaluation in HGSOC patients. Given that measurement of homologous recombination deficiency (HRD) is extremely complex molecular analysis is outsourced. Of note, this diagnostic algorithm is affected by inconclusive results and high rejection rates. Here, we review the molecular results of BRCA1/2 and HRD analysis from referral institution in predictive molecular pathology.

Methods: From May 2023 to Jan 2024 molecular records from 147 HGSOC patients simultaneously tested for BRCA1/2 and HRD measurement were inspected. A commercially available next-generation sequencing (NGS) panel (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) was adopted to internally perform molecular analysis on formalin-fixed paraffin-embedded (FFPE) samples. In a subset of patients clinical records were matched with molecular results.

Results: Overall, 2 out of 147 (1.3%) cases were morphologically classified as inadequate. Simultaneous BRCA1/2 - HRD analysis was successfully assessed in 112 out of 145 (77.2%) patents. Molecular analysis revealed 7 out of 112 (6.2%) and 2 out of 112 (1.8%) pathogenetic or likely pathogenetic (class I-II) and variants of uncertain significance (VUS) (class III) BRCA1/2 molecular alterations, respectively. HRD score was positive in 48 out of 112 (42.8%) HGSOC patients.

Conclusions: HRD testing is a reliable method for the clinical management of HGSOC patients.