RT Journal Article
SR Electronic
T1 In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 478
OP 485
DO 10.1136/jcp-2023-208852
VO 77
IS 7
A1 Pepe, Francesco
A1 Guerini-Rocco, Elena
A1 Fassan, Matteo
A1 Fusco, Nicola
A1 Vacirca, Davide
A1 Ranghiero, Alberto
A1 Venetis, Konstantinos
A1 Rappa, Alessandra
A1 Taormina, Sergio Vincenzo
A1 Russo, Gianluca
A1 Rebellato, Elena
A1 Munari, Giada
A1 Moreno-Manuel, Andrea
A1 De Angelis, Carmine
A1 Zamagni, Claudio
A1 Valabrega, Giorgio
A1 Malapelle, Umberto
A1 Troncone, Giancarlo
A1 Barberis, Massimo
A1 Iaccarino, Antonino
YR 2024
UL http://jcp.bmj.com/content/77/7/478.abstract
AB 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.Data are available on request to the corresponding author. All data relevant to the study are included in the article or uploaded as supplementary information All data that are publicly available and used in the writing of this article in the text and the reference list.