ArticleThe Journal of clinical endocrinology and metabolism2023
Molecular Profiling of 50 734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management.
Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2025Guideline
- Cytologic and Surgical Correlation ofInternational journal of surgical pathology · 2026Article
- Development of Novel mRNA Classifiers to Stratify Preoperative Thyroid Tumor Risk.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- Design and analytical validation of Nexthyro 2.0, a custom next-generation sequencing panel integrating DNA mutation profiling and RNA fusion detection for routine thyroid pathology specimens.Virchows Archiv : an international journal of pathology · 2026Article
- Afirma genomic sequencing classifier performance in young patients with cytologically indeterminate thyroid nodules.The Journal of clinical endocrinology and metabolism · 2026Article
- The Role of Cytology, Histology and Molecular Pathology in the Diagnostic Process of Thyroid Nodules.Cancers · 2026Review
- Diagnostic Utility of a Cost-Effective Four-Gene Next Generation Sequencing Panel for Predicting Papillary Thyroid Carcinoma in Indeterminate Thyroid Cytology: A Multicenter Study in China.Cancer medicine · 2026Article
- Analysis of PLEKHS1 promoter mutation in preoperative thyroid nodule samples.Cancer cytopathology · 2026Article
- A targeted proteomics assay for the preoperative diagnosis of thyroid nodules.Cell reports. Medicine · 2026Article
- Multidisciplinary team diagnosis and treatment of well-differentiated thyroid carcinoma: current landscape and future prospects.The oncologist · 2026Review
- Impact of reflexive preoperative molecular testing for indeterminate nodules on lobectomy and completion thyroidectomy rates.European thyroid journal · 2026Article
- Utility of Cell-Free DNA integrity index in differentiating malignant from benign lesions in indeterminate thyroid nodules.Endocrine · 2026Article
- Guiding Management of Bethesda V Thyroid Nodules: The Role of Molecular Testing.Clinical endocrinology · 2026Article
- Comparing the diagnostic accuracy of pre-operative genetic testing for thyroid cancer on fine needle aspiration cytology specimens: a systematic review and meta-analysis of diagnostic accuracy.Discover oncology · 2025Article
- Disease-Specific and Histological Outcomes of Preoperative TERT Promoter Mutation Detected in Isolation or in Combination with Other Mutations in Thyroid Neoplasms.Thyroid : official journal of the American Thyroid Association · 2025Article
- Pathological Diagnosis of Thyroid Nodules with Preoperatively DetectedThyroid : official journal of the American Thyroid Association · 2025Article
- Molecular Diagnostics and Personalized Therapeutics in Differentiated Thyroid Carcinoma: A Clinically Oriented Review.Diagnostics (Basel, Switzerland) · 2025Review
- Risk factors for lateral neck lymph node metastasis in papillary thyroid ultra micro carcinoma with implications for active surveillance.Scientific reports · 2025Article
- Mutational Profiling Detection in FNAC Samples of Different Types of Thyroid Neoplasms Using Targeted NGS.Cancers · 2025Article
- Approach to the Pediatric Patient With Thyroid Nodules.The Journal of clinical endocrinology and metabolism · 2025Review
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24 authors at 15 institutions in 1 country.
Funding
Abstract
contextComprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported.
objectiveTo determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules.
methodsThis retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients.
resultsAmong 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases.
conclusionIn this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.