Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments

(AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of , , and (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for...

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Bibliographic Details
Published in:Cancers 2023-12, Vol.15 (24), p.5843
Main Authors: Viscuse, Paul V, Slack-Tidwell, Rebecca S, Zhang, Miao, Rohra, Prih, Zhu, Keyi, San Lucas, F Anthony, Konnick, Eric, Pilie, Patrick G, Siddiqui, Bilal, Logothetis, Christopher J, Corn, Paul, Subudhi, Sumit K, Pritchard, Colin C, Soundararajan, Rama, Aparicio, Ana
Format: Article
Language:English
Subjects:
Androgens
Antibodies
Biomarkers
Biopsy
Cancer
Care and treatment
Chemotherapy
Clinical trials
Copy number
Deoxyribonucleic acid
DNA
Genes
Genomes
Immunohistochemistry
Laboratories
Medical laboratories
Medical research
Medicine, Experimental
Metastases
Metastasis
Mutation
Next-generation sequencing
p53 Protein
Patients
Prostate cancer
PTEN protein
Solid tumors
Tumor cells
Tumor proteins
Tumors
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Summary:(AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of , , and (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 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 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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15245843