The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks
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...
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2994 |
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| author | Lise M. van Wijk 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 Maaike P. G. Vreeswijk |
| author_facet | Lise M. van Wijk 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 Maaike P. G. Vreeswijk |
| author_sort | Lise M. van Wijk |
| collection | DOAJ |
| description | 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 <i>n</i> = 25) and epithelial ovarian cancer (OC <i>n</i> = 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 <i>ex vivo</i> irradiation of fresh tissue (RECAP test). The RAD51-FFPE test detected <i>BRCA</i> 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. |
| first_indexed | 2024-03-10T10:23:28Z |
| format | Article |
| id | doaj.art-5c7e5eef71a44a0eac94c873b0137992 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:23:28Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5c7e5eef71a44a0eac94c873b01379922023-11-22T00:13:00ZengMDPI AGCancers2072-66942021-06-011312299410.3390/cancers13122994The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor BlocksLise M. van Wijk0Claire J. H. Kramer1Sylvia Vermeulen2Natalja T. ter Haar3Marthe M. de Jonge4Judith R. Kroep5Cor D. de Kroon6Katja N. Gaarenstroom7Harry Vrieling8Tjalling Bosse9Maaike P. G. Vreeswijk10Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Medical Oncology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Gynecology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Gynecology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsPARP 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 <i>n</i> = 25) and epithelial ovarian cancer (OC <i>n</i> = 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 <i>ex vivo</i> irradiation of fresh tissue (RECAP test). The RAD51-FFPE test detected <i>BRCA</i> 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.https://www.mdpi.com/2072-6694/13/12/2994endometrial carcinomaovarian carcinomahomologous recombination deficiencyRECAP testRAD51-FFPE testRAD51 |
| spellingShingle | Lise M. van Wijk 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 Maaike P. G. Vreeswijk The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks Cancers endometrial carcinoma ovarian carcinoma homologous recombination deficiency RECAP test RAD51-FFPE test RAD51 |
| title | The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks |
| title_full | The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks |
| title_fullStr | The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks |
| title_full_unstemmed | The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks |
| title_short | The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks |
| title_sort | rad51 ffpe test calibration of a functional homologous recombination deficiency test on diagnostic endometrial and ovarian tumor blocks |
| topic | endometrial carcinoma ovarian carcinoma homologous recombination deficiency RECAP test RAD51-FFPE test RAD51 |
| url | https://www.mdpi.com/2072-6694/13/12/2994 |
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