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Volume 13
Issue 12
10.3390/cancers13122994
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Article

The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks

by
Lise M. van Wijk
1,
Claire J. H. Kramer
2,
Sylvia Vermeulen
1,
Natalja T. ter Haar
2,
Marthe M. de Jonge
2,
Judith R. Kroep
3,
Cor D. de Kroon
4,
Katja N. Gaarenstroom
4,
Harry Vrieling
1,
Tjalling Bosse
2 and
Maaike P. G. Vreeswijk
1,*
1
Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
2
Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
3
Department of Medical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
4
Department of Gynecology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: David Wong
Cancers 2021, 13(12), 2994; https://doi.org/10.3390/cancers13122994
Received: 5 May 2021 / Revised: 8 June 2021 / Accepted: 11 June 2021 / Published: 15 June 2021
(This article belongs to the Special Issue Homolog Recombination Deficiency, Genetics in Ovarian Cancer)
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Simple Summary

Rapid and reliable identification of patients with homologous recombination deficient (HRD) tumors is important for treatment choice as these tumors tend to respond well to platinum-based chemotherapy and PARP inhibitors (PARPi). In this study, a RAD51-based functional HRD test that can be performed on routine diagnostic formalin-fixed paraffin-embedded (FFPE) tissues (RAD51-FFPE test), was further improved and optimal test parameters were determined. The RAD51-FFPE test was able to determine tumor HR status with high sensitivity and specificity, making it an attractive test to be applied as routine diagnostic tool in the near future.

Abstract

PARP inhibitor (PARPi) sensitivity is related to tumor-specific defects in homologous recombination (HR). Therefore, there is great clinical interest in tests that can rapidly and reliably identify HR deficiency (HRD). Functional HRD tests determine the actual HR status by using the (dis)ability to accumulate RAD51 protein at sites of DNA damage as read-out. In this study, we further improved and calibrated a previously described RAD51-based functional HRD test on 74 diagnostic formalin-fixed paraffin-embedded (FFPE) specimens (RAD51-FFPE test) from endometrial cancer (EC n = 25) and epithelial ovarian cancer (OC n = 49) patients. We established optimal parameters with regard to RAD51 foci cut-off (≥2) and HRD threshold (15%) using matched endometrial and ovarian carcinoma specimens for which HR status had been established using a RAD51-based test that required ex vivo irradiation of fresh tissue (RECAP test). The RAD51-FFPE test detected BRCA deficient tumors with 90% sensitivity and RECAP-HRD tumors with 87% sensitivity, indicating that it is an attractive alternative to DNA-based tests with the potential to be applied in routine diagnostic pathology.
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Keywords: endometrial carcinoma; ovarian carcinoma; homologous recombination deficiency; RECAP test; RAD51-FFPE test; RAD51; BRCA1; BRCA2 endometrial carcinoma; ovarian carcinoma; homologous recombination deficiency; RECAP test; RAD51-FFPE test; RAD51; BRCA1; BRCA2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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MDPI and ACS Style

van Wijk, L.M.; Kramer, C.J.H.; Vermeulen, S.; ter Haar, N.T.; de Jonge, M.M.; Kroep, J.R.; de Kroon, C.D.; Gaarenstroom, K.N.; Vrieling, H.; Bosse, T.; Vreeswijk, M.P.G. The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks. Cancers 2021, 13, 2994. https://doi.org/10.3390/cancers13122994

AMA Style

van Wijk LM, Kramer CJH, Vermeulen S, ter Haar NT, de Jonge MM, Kroep JR, de Kroon CD, Gaarenstroom KN, Vrieling H, Bosse T, Vreeswijk MPG. The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks. Cancers. 2021; 13(12):2994. https://doi.org/10.3390/cancers13122994

Chicago/Turabian Style

van Wijk, Lise M., Claire J.H. Kramer, Sylvia Vermeulen, Natalja T. ter Haar, Marthe M. de Jonge, Judith R. Kroep, Cor D. de Kroon, Katja N. Gaarenstroom, Harry Vrieling, Tjalling Bosse, and Maaike P.G. Vreeswijk. 2021. "The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks" Cancers 13, no. 12: 2994. https://doi.org/10.3390/cancers13122994

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