False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology

Objective: This study aimed to assess the false negative rate (FNR) and concordance of pre-operative ThyGeNEXT®+ThyraMIR® testing in Bethesda category III-V thyroid nodules by comparing results with post-surgical histopathology in thyroid cancer. Methods: A retrospective review was conducted on 19 p...

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Main Authors: Sobrina S. Mohammed, Daniel Mettman, Mariana Garcia-Touza, Maricel Ridella, Betty Drees
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Journal of Clinical & Translational Endocrinology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214623725000146
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author Sobrina S. Mohammed
Daniel Mettman
Mariana Garcia-Touza
Maricel Ridella
Betty Drees
author_facet Sobrina S. Mohammed
Daniel Mettman
Mariana Garcia-Touza
Maricel Ridella
Betty Drees
author_sort Sobrina S. Mohammed
collection DOAJ
description Objective: This study aimed to assess the false negative rate (FNR) and concordance of pre-operative ThyGeNEXT®+ThyraMIR® testing in Bethesda category III-V thyroid nodules by comparing results with post-surgical histopathology in thyroid cancer. Methods: A retrospective review was conducted on 19 patients with Bethesda III-V thyroid nodules who underwent ThyGeNEXT®+ThyraMIR® testing followed by total thyroidectomy with histopathology confirming thyroid cancer. Fine needle aspiration (FNA) cytology, molecular test results, post-surgical histopathology and comprehensive genomic profiling reports (when available) were examined. Concordance was assessed by comparing pre-operative test results (mutations or malignant miRNA expression) to post-surgical histopathology. Discrepancies were further explored using Tempus xT genomic profiling for additional mutations and evaluation of tumor heterogeneity. The FNR was calculated accordingly. Results: FNR was 10.5 % and there was a high positive concordance with 89.5 % of cases testing positive for mutations or malignant miRNA classifiers. TERT c.-146C>T, NRAS Q61R, and BRAF V600E were among mutations identified. Comprehensive genomic profiling clarified false negatives, revealing insights into the impact of tumor heterogeneity. The miRNA classifier proved effective in detecting malignancy, in cases with subthreshold and RAS mutations or without common genetic alterations. Reliable results were obtained from diverse specimen types. Conclusions: The low false-negative rate and positive concordance with histopathology highlights the utility of ThyGeNEXT® + ThyraMIR® in enhancing risk stratification and guiding personalized management of indeterminate thyroid nodules and thyroid cancer.
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spelling doaj-art-b6ca38bcbcbb41678a87333a98ca38eb2025-08-20T03:55:17ZengElsevierJournal of Clinical & Translational Endocrinology2214-62372025-06-014010039610.1016/j.jcte.2025.100396False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathologySobrina S. Mohammed0Daniel Mettman1Mariana Garcia-Touza2Maricel Ridella3Betty Drees4University of Missouri-Kansas City School of Medicine, Division of Endocrinology, Department of Internal Medicine, 2301 Holmes Street, Kansas City, MO 64108, USA; Corresponding author at: Division of Endocrinology, Department of Internal Medicine, University of Missouri-Kansas City School of Medicine, 2301 Holmes Street, Kansas City, MO 64108, USA.Kansas City Veterans Affairs Medical Center, Department of Pathology, 4801 Linwood Blvd, Kansas City, MO 64128, USAKansas City Veterans Affairs Medical Center, Department of Endocrinology, 4801 Linwood Blvd, Kansas City, MO 64128, USAKansas City Veterans Affairs Medical Center, Department of Endocrinology, 4801 Linwood Blvd, Kansas City, MO 64128, USAUniversity of Missouri-Kansas City School of Medicine, Division of Endocrinology, Department of Internal Medicine, 2301 Holmes Street, Kansas City, MO 64108, USA; Graduate School of the Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USAObjective: This study aimed to assess the false negative rate (FNR) and concordance of pre-operative ThyGeNEXT®+ThyraMIR® testing in Bethesda category III-V thyroid nodules by comparing results with post-surgical histopathology in thyroid cancer. Methods: A retrospective review was conducted on 19 patients with Bethesda III-V thyroid nodules who underwent ThyGeNEXT®+ThyraMIR® testing followed by total thyroidectomy with histopathology confirming thyroid cancer. Fine needle aspiration (FNA) cytology, molecular test results, post-surgical histopathology and comprehensive genomic profiling reports (when available) were examined. Concordance was assessed by comparing pre-operative test results (mutations or malignant miRNA expression) to post-surgical histopathology. Discrepancies were further explored using Tempus xT genomic profiling for additional mutations and evaluation of tumor heterogeneity. The FNR was calculated accordingly. Results: FNR was 10.5 % and there was a high positive concordance with 89.5 % of cases testing positive for mutations or malignant miRNA classifiers. TERT c.-146C>T, NRAS Q61R, and BRAF V600E were among mutations identified. Comprehensive genomic profiling clarified false negatives, revealing insights into the impact of tumor heterogeneity. The miRNA classifier proved effective in detecting malignancy, in cases with subthreshold and RAS mutations or without common genetic alterations. Reliable results were obtained from diverse specimen types. Conclusions: The low false-negative rate and positive concordance with histopathology highlights the utility of ThyGeNEXT® + ThyraMIR® in enhancing risk stratification and guiding personalized management of indeterminate thyroid nodules and thyroid cancer.http://www.sciencedirect.com/science/article/pii/S2214623725000146Thyroid nodulesMolecular testingThyGeNEXT+ThyraMIRFalse negative rateHistopathologymiRNA profiling
spellingShingle Sobrina S. Mohammed
Daniel Mettman
Mariana Garcia-Touza
Maricel Ridella
Betty Drees
False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology
Journal of Clinical & Translational Endocrinology
Thyroid nodules
Molecular testing
ThyGeNEXT+ThyraMIR
False negative rate
Histopathology
miRNA profiling
title False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology
title_full False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology
title_fullStr False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology
title_full_unstemmed False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology
title_short False negative rate and concordance of ThyGeNEXT®+ThyraMIR® testing with post-thyroidectomy histopathology
title_sort false negative rate and concordance of thygenext r thyramir r testing with post thyroidectomy histopathology
topic Thyroid nodules
Molecular testing
ThyGeNEXT+ThyraMIR
False negative rate
Histopathology
miRNA profiling
url http://www.sciencedirect.com/science/article/pii/S2214623725000146
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