Sistema de Salut de Catalunya
Institut Català de la Salut
[Kramer CJ, Ter Haar NT] Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. [Llop-Guevara A, Herencia-Ropero A, Serra V] Grup de Terapèutica Experimental, Vall d'Hebron Institut d'Oncologia (VHIO), Barcelona, Spain. [Yaniz-Galende E] Department of Oncology, Institute Gustave Roussy, Villejuif, France. [Pellegrino B] Department of Medicine and Surgery, University of Parma, Parma, Italy. Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy
Vall d'Hebron Barcelona Hospital Campus
2023-10-16T08:32:16Z
2023-10-16T08:32:16Z
2023-11
Biomarker; High-hrade serous ovarian carcinoma; Homologous recombination deficiency
Biomarcador; Carcinoma de ovario seroso de alto grado; Deficiencia de recombinación homóloga
Biomarcador; Carcinoma d'ovari serós d'alt grau; Deficiència de recombinació homòloga
The RAD51 test is emerging as a promising biomarker for the assessment of functional homologous recombination deficiency (HRD). Yet, the robustness and reproducibility of the immunofluorescence-based RAD51 test, in different academic laboratories, have not been systematically investigated. Therefore, we tested the performance of the RAD51 assay in formalin-fixed paraffin-embedded (FFPE) high-grade serous ovarian carcinoma (HGSOC) samples in four European laboratories. Here, we confirm that subtle differences in staining procedures result in low variability of RAD51 and γH2AX scores. However, substantial variability in RAD51 scoring was observed in some samples, likely due to complicating technical and biological features, such as high RAD51 signal-to-noise ratio and RAD51 heterogeneity. These results support the need to identify and perform additional quality control steps and/or automating image analysis. Altogether, resolving technical issues should be a priority, as identifying tumours with functional HRD is urgently needed to guide the individual treatment of HGSOC patients. Follow-up studies are needed to define the key tissue quality requirements to assess HRD by RAD51 in FFPE tumour samples, as this test could help in guiding the individual treatment of HGSOC patients.
This work was supported by the Dutch Cancer Society (KWF) (grant: 12995 to TB and MV) and by ERA PerMed (grant ERAPERMED2019-215 to VS). VS received funding from Instituto de Salud Carlos III (CPII19/00033). ALG received funding from Asociación Española Contra el Cáncer (AECC) (INVES20095LLOP) and AHR from Generalitat de Catalunya (PERIS SLT017/20/000081).
Article
Published version
English
Ovaris - Càncer - Aspectes genètics; Marcadors tumorals; Recombinació genètica; DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms; PHENOMENA AND PROCESSES::Genetic Phenomena::Recombination, Genetic::Homologous Recombination; CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor; CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Recombinases::Rec A Recombinases::Rad51 Recombinase; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas; FENÓMENOS Y PROCESOS::fenómenos genéticos::recombinación genética::recombinación homóloga; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales; COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::recombinasas::rec a recombinasas::rad51 recombinasa
Wiley
The Journal of Pathology: Clinical Research;9(6)
https://doi.org/10.1002/cjp2.336
info:eu-repo/grantAgreement/ES/PE2017-2020/CPII19%2F00033
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
