In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study

J Clin Pathol. 2024 Jun 19;77(7):478-485. doi: 10.1136/jcp-2023-208852.


Aims: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) represent a standard of care for the clinical management of high-grade serous ovarian cancer (HGSOC). The recognition of homologous recombination deficiency (HRD) has emerged as a predictive biomarker of response for first-line PARPIs treatment in patients with HGOSC. On the other hand, this test is extremely complex and therefore it is often externalised. Regrettably, the reliability of outsourced HRD testing can be troubled by inconclusive results and high rejection rates. In this methodological study, we assessed the technical feasibility, interassay and interlaboratory reproducibility of in-house HRD testing using three different commercially available next-generation sequencing assays.

Methods: A total of n=20 epithelial ovarian cancer samples previously analysed with MyChoice CDx were subjected to HRD retesting using three different platforms in three different major pathology laboratories, that is, SOPHiA DDM HRD Solution, HRD focus and Oncomine homologous recombination repair pathway predesigned panel. Concordance was calculated by Cohen's (dual) and Fleiss (triple) κ coefficients.

Results: In-house BRCA1/2 molecular testing yielded a concordance rate >90.0% among all participating centres. HRD scores were successfully calculated by each institution with a concordance rate of 76.5%. Concerning the external gold standard test, the overall percentage of agreement ranged from 80.0% to 90.0% with a positive percentage agreement ranging from 75.0% to 80.0% and a negative percentage agreement ranging from 80.0% to 100%.

Conclusions: In-house testing for HRD can be reliably performed with commercially available next-generation sequencing assays.

Keywords: ovarian neoplasms; pathology, molecular; point-of-care testing.

Publication types

  • Multicenter Study

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Ovarian Epithelial / genetics
  • Feasibility Studies
  • Female
  • Genetic Testing / methods
  • High-Throughput Nucleotide Sequencing*
  • Homologous Recombination*
  • Humans
  • Italy
  • Ovarian Neoplasms* / genetics
  • Pilot Projects
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Reproducibility of Results


  • BRCA2 Protein
  • BRCA1 Protein
  • Poly(ADP-ribose) Polymerase Inhibitors
  • BRCA1 protein, human
  • BRCA2 protein, human
  • Biomarkers, Tumor