Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments
<i>Aggressive-variant prostate cancers</i> (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of <i>TP53</i>, <i>RB1</i>, and <i>PTEN</i> (AVPCm), a profile linked to lineage plast...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/24/5843 |
| _version_ | 1797381654406234112 |
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| author | Paul V. Viscuse Rebecca S. Slack-Tidwell Miao Zhang Prih Rohra Keyi Zhu F. Anthony San Lucas Eric Konnick Patrick G. Pilie Bilal Siddiqui Christopher J. Logothetis Paul Corn Sumit K. Subudhi Colin C. Pritchard Rama Soundararajan Ana Aparicio |
| author_facet | Paul V. Viscuse Rebecca S. Slack-Tidwell Miao Zhang Prih Rohra Keyi Zhu F. Anthony San Lucas Eric Konnick Patrick G. Pilie Bilal Siddiqui Christopher J. Logothetis Paul Corn Sumit K. Subudhi Colin C. Pritchard Rama Soundararajan Ana Aparicio |
| author_sort | Paul V. Viscuse |
| collection | DOAJ |
| description | <i>Aggressive-variant prostate cancers</i> (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of <i>TP53</i>, <i>RB1</i>, and <i>PTEN</i> (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven (39%) based on ctDNA. The concordance of the IHC reads between pathologists was variable. IHC had a higher detection rate of AVPCm<sup>+</sup> tumors with the shortest turnaround times. stDNA had challenges with copy number loss detection, limiting its detection rate. ctDNA detected the greatest proportion of AVPCm<sup>+</sup> tumors but had a low tumor content in two thirds of patients. These data show the operational characteristics of AVPCm detection using various assays, and inform trial design using AVPCm as a criterion for patient selection or stratification. |
| first_indexed | 2024-03-08T20:55:33Z |
| format | Article |
| id | doaj.art-371ad1909395468281e7a1f356fed37b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T20:55:33Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-371ad1909395468281e7a1f356fed37b2023-12-22T13:59:02ZengMDPI AGCancers2072-66942023-12-011524584310.3390/cancers15245843Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) EnvironmentsPaul V. Viscuse0Rebecca S. Slack-Tidwell1Miao Zhang2Prih Rohra3Keyi Zhu4F. Anthony San Lucas5Eric Konnick6Patrick G. Pilie7Bilal Siddiqui8Christopher J. Logothetis9Paul Corn10Sumit K. Subudhi11Colin C. Pritchard12Rama Soundararajan13Ana Aparicio14Department of Medicine, University of Virginia, Charlottesville, VA 22903, USADepartment of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USADepartment of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USADepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA<i>Aggressive-variant prostate cancers</i> (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of <i>TP53</i>, <i>RB1</i>, and <i>PTEN</i> (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven (39%) based on ctDNA. The concordance of the IHC reads between pathologists was variable. IHC had a higher detection rate of AVPCm<sup>+</sup> tumors with the shortest turnaround times. stDNA had challenges with copy number loss detection, limiting its detection rate. ctDNA detected the greatest proportion of AVPCm<sup>+</sup> tumors but had a low tumor content in two thirds of patients. These data show the operational characteristics of AVPCm detection using various assays, and inform trial design using AVPCm as a criterion for patient selection or stratification.https://www.mdpi.com/2072-6694/15/24/5843aggressive-variant prostate cancerimmunohistochemistrymolecular biomarkernext-generation sequencing |
| spellingShingle | Paul V. Viscuse Rebecca S. Slack-Tidwell Miao Zhang Prih Rohra Keyi Zhu F. Anthony San Lucas Eric Konnick Patrick G. Pilie Bilal Siddiqui Christopher J. Logothetis Paul Corn Sumit K. Subudhi Colin C. Pritchard Rama Soundararajan Ana Aparicio Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments Cancers aggressive-variant prostate cancer immunohistochemistry molecular biomarker next-generation sequencing |
| title | Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments |
| title_full | Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments |
| title_fullStr | Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments |
| title_full_unstemmed | Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments |
| title_short | Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments |
| title_sort | evaluation of the aggressive variant prostate cancer molecular signature in clinical laboratory improvement amendments clia environments |
| topic | aggressive-variant prostate cancer immunohistochemistry molecular biomarker next-generation sequencing |
| url | https://www.mdpi.com/2072-6694/15/24/5843 |
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