Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules

Nikiforova, Marina N.; Mercurio, Stephanie; Wald, Abigail I.; Moura, Michelle Barbi de; Callenberg, Keith M.; Santana-Santos, Lucas; Gooding, William E.; Yip, Linwah; Ferris, Robert L.; Nikiforov, Yuri E.

doi:10.1002/cncr.31245

Cited by 296 publications

(316 citation statements)

References 25 publications

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“…These markers have been tested both individually and in panels even though only some of them (BRAF V600E mutation and RET/PCT rearrangements) show high specificity and likelihood of a malignant diagnosis in mutated thyroid lesions. Molecular thyroid tests that are commercially available in the United States are: 1) ThyroSeq (University of Pittsburgh Medical Center/Cytopath Biopsy Lab, Pittsburgh, PA), 2) Afirma Gene Expression Classifier (GEC; Veracyte, South San Francisco, CA), 3) RosettaGX Reveal (Rosetta Genomics, Philadelphia, PA), and 4) ThyGenX and ThyraMIR (both from Interpace Diagnostics, Parsippany, NJ) . Whereas the Thyroseq and ThyGenX tests have high positive predictive value (PPV) and negative predictive value (NPV) wherein high PPV helps as a “rule‐in malignancy” test, the Afirma GEC with its high NPV helps as a “rule‐out malignancy” test mostly for indeterminate thyroid lesions .…”

Section: Molecular Profiling Of Thyroid Lesionsmentioning

confidence: 99%

“…This recent acknowledgement of the role of molecular testing formalizes their use in defining risk stratification of patients with thyroid nodules. In this review, we discuss the clinical implications of the different molecular tests in the indeterminate Bethesda categories . It is important to note that the literature to date generally supports employing a combination of morphology and molecular testing to best guide the clinical or surgical approach for patients diagnosed with indeterminate thyroid nodules (Table ).…”

Section: Molecular Test Options and Molecular Approach To Indeterminamentioning

confidence: 99%

“…The ThyroSeq v.3 test now includes 112 genes in the panel, in which 5 classes of genetic alterations are detected. The test analyzes more than 12,000 mutation hotspots and more than 120 gene fusion types, which were validated in a cohort of 238 tissue samples and 175 FNAC cases with known follow‐up . In the FNA validation set, the sensitivity was 98.0%, the specificity was 81.8%, and the accuracy was 90.9%.…”

Section: Molecular Testing and The Indeterminate Categories (Aus/flusmentioning

confidence: 99%

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Ancillary molecular testing of indeterminate thyroid nodules

Rossi

Larocca

Pantanowitz

2018

Cancer Cytopathology

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Cytological specimens from thyroid nodules are increasingly being adopted as the first available material for cost effectively managing patients in the era of personalized medicine. Cytology aspirates not only play a central role in providing accurate diagnoses, but are also being collected for ancillary molecular testing. Molecular analysis, including the evaluation of somatic mutations and other genomic alterations, has accordingly become well integrated in the cytological workup of thyroid lesions. Appropriately handled thyroid cytology preparations provide well-preserved and adequately cellular material with improved DNA/RNA quantity. The recent publication of the 2nd edition of The Bethesda System for Reporting Thyroid Cytopathology and the American Thyroid Association guidelines confirm the relevant role of molecular testing in the management of the different subcategories of indeterminate thyroid lesions. This review discusses the role of molecular testing for indeterminate thyroid nodules, including the recent introduction of the noninvasive, encapsulated follicular variant of papillary thyroid carcinoma (FVPTC), known also as noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP).

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Section: Molecular Profiling Of Thyroid Lesionsmentioning

confidence: 99%

Section: Molecular Test Options and Molecular Approach To Indeterminamentioning

confidence: 99%

Section: Molecular Testing and The Indeterminate Categories (Aus/flusmentioning

confidence: 99%

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Ancillary molecular testing of indeterminate thyroid nodules

Rossi

Larocca

Pantanowitz

2018

Cancer Cytopathology

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“…ThyroSeq v3 is an updated NGS molecular platform that tests for additional genetic alterations including copy number alterations (CNA). The reported sensitivity and specificity for distinguishing a benign from a cancerous thyroid nodule was 93.9% and 89.4%, respectively, with an overall accuracy of 92.1% …”

Section: Introductionmentioning

confidence: 99%

Hürthle cell lesions on thyroid fine needle aspiration cytology: Molecular and histologic correlation

Schatz-Siemers

Brandler

Oweity

et al. 2019

Diagnostic Cytopathology

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Background Hürthle cell lesions often pose diagnostic challenges, despite their common occurrence on thyroid fine‐needle aspiration cytology (FNAC). The associated molecular alterations are also not well understood. Therefore, our study aimed to delineate the molecular profile of Hürthle cell lesions classified as Bethesda Categories III or IV (atypia of undetermined significance (AUS) or suspicious for follicular neoplasm (SFN)) on FNAC and to correlate this molecular profile with surgical resection findings. Methods This study consisted of 188 Hürthle cell lesions with indeterminate cytology and ThyroSeq® v2/v3 molecular testing results. Surgical follow‐up was available for 33 cases. Results The majority of indeterminate Hürthle cell lesions had negative ThyroSeq® results (61%) and were benign on available surgical follow‐up. The most prevalent mutations involved the RAS gene (21%), which were associated with benign lesions, non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features (NIFTP), and malignancy. The remaining mutations involved less than 18% of the cases, including PAX8/PPARG (3.7%), TSHR (3.7%), EIF1AX (2.7%), MET (2.1%), PTEN (1.6%), clonal copy number alteration (1.6%), TERT (1.1%), and 0.5% each of GNAS, PIK3CA, and TP53 mutations. On follow‐up, 45% were benign, 24% were NIFTP, and 30% were malignant. The malignant cases had different molecular alterations. Conclusion No single molecular alteration defines cytologically indeterminate Hürthle cell lesions; the majority of cases have low‐risk or no molecular alterations and are benign on follow‐up. These findings suggest that molecular testing may be useful, but is not definitive, in determining which cases may be managed conservatively; additional studies are needed to fully determine the negative predictive value in ruling out malignancy.

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“…Molecular testing was just beginning to appear on the FNA scene about 5 years ago and was essentially a research test. That is no longer so with the recent announcement of what is effectively the third generation of testing . What we are witnessing now is the FNA molecular testing version of Moore’s law, which describes the doubling of computer capacity every year .…”

Section: Fna Molecular Testing Now and In The Futurementioning

confidence: 99%

Private practice outpatient fine needle aspiration clinic: A 2018 update

Abele

2018

Cancer Cytopathology

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This review updates a 2008 report on the establishment of a pathologist‐directed ultrasound‐guided fine needle aspiration (USGFNA) biopsy clinic in a private practice setting. During this time, ultrasound evaluation of the thyroid has evolved from simply sampling a nodule to a reliable cancer risk assessment (CRA). Because of perceived poor reliability in many local radiology thyroid ultrasound reports, first endocrinologists and then pathologists began performing their own ultrasound evaluations, cancer risk assessments, and USGFNAs. The present review covers a wide range of topics, including incorporating ultrasound data into a report, the uniqueness of the thyroid as an USGFNA target, artifact pseudocomplexity mimicking neoplasia, the pathologist’s ability to acquire thyroid cancer risk assessment expertise, and distinguishing a true thyroid nodule from a pseudonodule with appropriate documentation. The use of ultrasound does not change the core need for high‐level biopsy and smear‐making techniques. Two national courses offer advanced training and certification. Selection of mission‐appropriate ultrasound machines is discussed along with the pitfalls of purchase. Determining the location of a USGFNA clinic requires several considerations, as does the layout detail of the clinic interior for optimal patient comfort and experience. Ultrasound does not obviate the pathologist’s anticipation of patient concerns or of providing information, including revealing a cancer diagnosis. The goal of this review is to help guide the reader to successfully and beneficially bring the science of USGFNA to patients in an understandable and caring way.

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Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules

Cited by 296 publications

References 25 publications

Ancillary molecular testing of indeterminate thyroid nodules

Ancillary molecular testing of indeterminate thyroid nodules

Hürthle cell lesions on thyroid fine needle aspiration cytology: Molecular and histologic correlation

Private practice outpatient fine needle aspiration clinic: A 2018 update

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