Afirma Genomic Sequencing Classifier and Xpression Atlas Molecular Findings in Consecutive Bethesda III-VI Thyroid Nodules

作者：Mimi I-Nan Hu, Steven G. Waguespack, Chrysoula Dosiou, Paul W. Ladenson, Masha Jean Livhits, Lori J. Wirth, Peter M. Sadow, Jeffrey F. Krane, Brendan C. Stack, Mark Zafereo, Syed Zulfiqar Ali, Steven P. Weitzman, Yangyang Hao, Joshua Babiarz, Giulia Catignani Kennedy, Richard T. Kloos · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2021 · DOI：10.1210/clinem/dgab304 · 被引用次数：67 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Thyroid Disorders and Treatments、Thyroid and Parathyroid Surgery

CONTEXT: Broad genomic analyses among thyroid histologies have been described from relatively small cohorts. OBJECTIVE: Investigate the molecular findings across a large, real-world cohort of thyroid fine-needle aspiration (FNA) samples. DESIGN: Retrospective analysis of RNA sequencing data files. SETTING: Clinical Laboratory Improvement Amendments laboratory performing Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas (XA) testing. PARTICIPANTS: A total of 50 644 consecutive Bethesda III-VI nodules. INTERVENTION: None. MAIN OUTCOME MEASURES: Molecular test results. RESULTS: Of 48 952 Bethesda III/IV FNAs studied, 66% were benign by Afirma GSC. The prevalence of BRAF V600E was 2% among all Bethesda III/IV FNAs and 76% among Bethesda VI FNAs. Fusions involving NTRK, RET, BRAF, and ALK were most prevalent in Bethesda V (10%), and 130 different gene partners were identified. Among small consecutive Bethesda III/IV sample cohorts with one of these fusions and available surgical pathology excision data, the positive predictive value of an NTRK or RET fusion for carcinoma or noninvasive follicular thyroid neoplasm with papillary-like nuclear features was >95%, whereas for BRAF and ALK fusions it was 81% and 67%, respectively. At least 1 genomic alteration was identified by the expanded Afirma XA panel in 70% of medullary thyroid carcinoma classifier-positive FNAs, 44% of Bethesda III or IV Afirma GSC suspicious FNAs, 64% of Bethesda V FNAs, and 87% of Bethesda VI FNAs....