Molecular Classification of Thyroid Nodules Using High-Dimensionality Genomic Data

Chudova, Darya; Wilde, Jonathan I.; Wang, Eric T.; Wang, Hui; Rabbee, Nusrat; Egidio, Camila; Reynolds, Jessica; Tom, Edward; Pagan, Moraima; Rigl, C. Ted; Friedman, Lyssa; Wang, C. Charles; Lanman, Richard B.; Zeiger, Martha A.; Kebebew, Electron; Rosaí, Juan; Fellegara, Giovanni; LiVolsi, Virginia A.; Kennedy, Giulia C.

doi:10.1210/jc.2010-1087

Cited by 248 publications

(159 citation statements)

References 28 publications

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“…The selected gene profile is based on the gene expression identified from FNAs of surgically proven benign and malignant thyroid nodules. 12,13 Only FNA lesions designated as FLUS/AUS and (suspicious for) Hürthle/follicular neoplasm are accepted for analysis. Two dedicated FNA passes are collected from each thyroid nodule and immediately stored in a proprietary nucleic acid preservative solution.…”

Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Zhang

Lin²

2016

Archives of Pathology &Amp; Laboratory Medicine

100

158

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Context.— Fine-needle aspiration of thyroid nodules is a reliable diagnostic method to determine the nature of thyroid nodules. Nonetheless, indeterminate cytology diagnoses remain a diagnostic challenge. The development of multiplex molecular techniques and the identification of genetic alterations associated with different follicular cell–derived cancers in the thyroid have led to the introduction of several commercially available tests. Objective.— To summarize the most common commercially available molecular testing in thyroid cancer, focusing on the technical features and test performance validation. Data Sources.— Peer-reviewed original articles, review articles, and published conference abstracts were reviewed to analyze the advantages and limitations of the most common tests used in the evaluation of thyroid needle aspirations. Conclusions.— The most common tests available include the Afirma Gene Expression Classifier, ThyGenX, and ThyroSeq. The excellent negative predictive value (NPV) of the Afirma test allows it to be used as a “rule out” test. ThyGenX analyzes a panel of DNA mutations and RNA translocation fusion markers to assess the risk of malignancy with good NPV and positive predictive value. ThyroSeq is a next-generation sequencing–based gene mutation and fusion test that has been reported to have the best NPV and positive predictive value combined, suggesting that it can be used as a “rule in” and “rule out” test. Molecular testing of cytology specimens from thyroid nodules has the potential to play a major role in the evaluation of indeterminate thyroid lesions.

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Section: Afirma Gene Expression Classifiermentioning

confidence: 99%

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Zhang

Lin²

2016

Archives of Pathology &Amp; Laboratory Medicine

100

158

View full text Add to dashboard Cite

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“…Upregulation or aberrant expression of HMGA2, MET, TPO, TIMP1, DPP4, TFF3, SERPINA1, TIMP1, FN1, TGFA, CRABP1, FCGBP, EPS8 and PROS1 genes have been detected in malignant thyroid tumors [215][216][217][218][219][220]. Diagnostic use of expression levels and profiles of multiple genes have been tested and it is reported that the sensitivity and specificity of these techniques in differential diagnosis of malignant and benign thyroid nodules were 92% and 84%, respectively [221]. Mathur et al have explored the diagnostic utility of combined use of mutational analysis, gene expression profiling and classical cytological evaluation of FNAB samples [222].…”

Section: Molecular Targets In Histopathological Diagnosis and Classifmentioning

confidence: 99%

An update on molecular biology of thyroid cancers

Ömür

Baran

2014

Critical Reviews in Oncology/Hematology

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“…The initial publication included test validation on an independent sample set of cytologically indeterminate thyroid nodule FNAs with a prospective multicenter, double blind study design (44). The Afirma GEC achieved high sensitivity and NPV.…”

Section: Clinical Validitymentioning

confidence: 99%

Molecular markers in the diagnosis of thyroid nodules

Ward

Kloos²

2013

Arq Bras Endocrinol Metab

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SUMMARYAn indeterminate thyroid nodule cytology result occurs about every sixth fine-needle aspiration. These indeterminate nodules harbor a 24% risk of malignancy (ROM); too high to ignore, but driving surgery where most nodules are benign. Molecular diagnostics have emerged to ideally avoid surgery when appropriate, and to trigger the correct therapeutic surgery when indicated, as opposed to an incomplete diagnostic surgery. No current molecular test offers both high sensitivity and high specificity. A molecular diagnostic test with high sensitivity (e.g. Afirma Gene Expression Classifier sensitivity 90%) offers a high Negative Predictive Value when the ROM is relatively low, such as < 30%. Only such tests can "rule-out" cancer. In this setting, a molecularly benign result suggests the same ROM as that of operated cytologically benign nodules (~6%). Thus, clinical observation can replace diagnostic surgery; increasing quality of life and decreasing medical costs. However, its low specificity cannot "rule-in" cancer as a suspicious result has a Positive Predictive Value (PPV) of ~40%, perhaps too low to routinely reflex to definitive cancer surgery. Conversely, high specificity tests (BRAF, RAS, PPAR/PAX-8, RET/PTC, PTEN) offer high PPV results, and only these tests can "rule-in" cancer. Here a positive molecular result warrants definitive therapeutic surgery. However, their low sensitivity cannot "rule-out" cancer and a negative molecular result cannot dissuade diagnostic surgery; limiting their cost-effectiveness. Whether or not there is a useful and cost-effective role to sequentially combine these approaches, or to modify existing approaches, is under investigation. Arq Bras Endocrinol Metab. 2013;57(2):89-97 Keywords Biopsy, fine-needle; DNA mutational analysis; gene expression; genomics; molecular diagnostic techniques SUMáRioResultados indeterminados na citologia de um nódulo tireoidiano ocorrem em cerca de um a cada seis punções aspirativas por agulha fina. Esses nódulos indeterminados apresentam risco de malignidade (RM) de cerca de 24%, um valor alto demais para ser ignorado e que leva à cirurgia em casos em que a maioria dos nódulos é benigna. O diagnóstico molecular é uma forma ideal de se evitar a cirurgia quando apropriado e de se levar ao correto procedimento cirúrgico terapêutico quando indicado, em oposição à cirurgia diagnóstica incompleta. Atualmente, não existem testes moleculares com alta sensibilidade e especificidade. Um teste molecular de alta sensibilidade (por exemplo, a sensibilidade do teste Afirma Gene Expression Classifier é de 90%) tem um alto Valor Preditivo Negativo quando o RM é relativamente baixo, por exemplo, < 30%. Apenas esses testes podem "excluir" o câncer. Nesse contexto, um resultado molecular benigno sugere o mesmo RM de nódulos com resultado benigno na citologia e operados (~6%). Assim, a observação clínica pode substituir a cirurgia diagnóstica, aumentando a qualidade de vida e diminuindo os custos médicos. Entretanto, a baixa especificidade não pode "incluir" o cân...

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Molecular Classification of Thyroid Nodules Using High-Dimensionality Genomic Data

Cited by 248 publications

References 28 publications

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

Molecular Testing of Thyroid Nodules: A Review of Current Available Tests for Fine-Needle Aspiration Specimens

An update on molecular biology of thyroid cancers

Molecular markers in the diagnosis of thyroid nodules

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