Mohammed Sobrina S, Mettman Daniel, Garcia-Touza Mariana, Ridella Maricel, Drees Betty
University of Missouri-Kansas City School of Medicine, Division of Endocrinology, Department of Internal 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, USA.
J Clin Transl Endocrinol. 2025 Apr 24;40:100396. doi: 10.1016/j.jcte.2025.100396. eCollection 2025 Jun.
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.
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.
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.
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.
本研究旨在通过将术前ThyGeNEXT®+ThyraMIR®检测结果与甲状腺癌术后组织病理学结果进行比较，评估贝塞斯达III-V类甲状腺结节的假阴性率（FNR）及一致性。
对19例患有贝塞斯达III-V类甲状腺结节且接受了ThyGeNEXT®+ThyraMIR®检测，随后进行全甲状腺切除术且组织病理学确诊为甲状腺癌的患者进行回顾性研究。检查了细针穿刺（FNA）细胞学、分子检测结果、术后组织病理学及综合基因组分析报告（如有）。通过比较术前检测结果（突变或恶性miRNA表达）与术后组织病理学来评估一致性。使用Tempus xT基因组分析进一步探索差异，以检测额外的突变并评估肿瘤异质性。据此计算FNR。
FNR为10.5%，89.5%的病例在突变或恶性miRNA分类检测中呈阳性，具有较高的阳性一致性。检测到的突变包括TERT c.-146C>T、NRAS Q61R和BRAF V600E。综合基因组分析明确了假阴性结果，揭示了肿瘤异质性的影响。miRNA分类在检测亚阈值和RAS突变病例或无常见基因改变的病例中的恶性肿瘤方面被证明是有效的。从不同标本类型中获得了可靠结果。
低假阴性率及与组织病理学的阳性一致性突出了ThyGeNEXT®+ThyraMIR®在加强风险分层以及指导不确定甲状腺结节和甲状腺癌的个性化管理方面的效用。
