Multi-Centre Italian Study Validates In-House HRD Testing as Reliable Alternative to Outsourced Assays
Three Italian pathology laboratories independently tested 20 ovarian cancer samples using three commercially available NGS assays for homologous recombination deficiency, comparing results against the gold-standard MyChoice CDx. BRCA1/2 concordance exceeded 90% across all centres, and overall HRD score agreement with the reference test ranged from 80% to 90%. The findings demonstrate that in-house HRD testing with off-the-shelf NGS panels is technically feasible and reproducible, offering laboratories an alternative to outsourcing this critical companion diagnostic.
The original study
In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study.
- Authors
- Pepe F, Guerini-Rocco E, Fassan M, Fusco N, Vacirca D, Ranghiero A, et al.
- Journal
- Journal of clinical pathology
- Type
- Journal Article, Multicenter Study
- PMID
- 37072171
Original abstract
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.