Analytical Performance Verification of a Molecular Diagnostic for Cytology-Indeterminate Thyroid Nodules

Walsh, P. Sean; Wilde, Jonathan I.; Tom, Edward; Reynolds, Jessica; Chen, Daphne C.; Chudova, Darya; Pagan, Moraima; Pankratz, Daniel G.; Wong, Michael Y.; Veitch, James; Friedman, Lyssa; Monroe, R. J.; Steward, David L.; Lupo, Mark A.; Lanman, Richard B.; Kennedy, Giulia C.

doi:10.1210/jc.2012-1923

Cited by 57 publications

(34 citation statements)

References 15 publications

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“…It is possible that our sample of 35 subjects was insufficiently large to show weak associations that exist; alternatively, given the mixed findings in the literature, it is possible that these findings are specific to particular patient cohorts and therefore not applicable to our subject population. Among the relatively newer diagnostic methods, genetic markers (32,(41)(42)(43)(44) and US elastography (33)(34)(35)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60) have been evaluated. A new molecular test, Afirma (Veracyte, South San Francisco, Calif) has shown promise for preoperative malignancy risk stratification for these nodules (32).…”

Section: Swe Findingsmentioning

confidence: 99%

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane

Samir¹,

Dhyani²,

Anvari

et al. 2015

Radiology

107

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Section: Swe Findingsmentioning

confidence: 99%

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane

Samir¹,

Dhyani²,

Anvari

et al. 2015

Radiology

107

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“…Extensive reagent and analytical performance studies were conducted to evaluate the reliability and reproducibility of the GEC under a variety of experimental and clinical conditions, with robust and highly reproducible results (43). Interfering substances including human blood and genomic DNA were not found to interfere with extraction or amplification steps of the assay.…”

Section: Analytical 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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“…The test provides a binary ''suspicious'' or ''benign'' result for triaging thyroid nodules that have indeterminate cytologic features. The assay has been validated on fine-needle aspiration (FNA) material for patients older than 21 years of age with a >1 cm thyroid nodule and a cytologic diagnosis of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) or suspicious for follicular neoplasm (SFN) (1,2) according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) (3). Based on the initial validation study, the AGEC is not recommended for cytologic diagnoses of benign or suspicious for malignancy (1).…”

Section: Introductionmentioning

confidence: 99%

Performance of the Afirma Gene Expression Classifier in Hürthle Cell Thyroid Nodules Differs from Other Indeterminate Thyroid Nodules

Brauner

Holmes

Krane

et al. 2015

Thyroid

111

128

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While 32% of tested patients declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC findings had unnecessary surgery, reflecting a substantially lower rate of malignancy from what was previously reported for all indeterminate nodules. Given the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or AFHCN, a suspicious AGEC diagnosis does not increase the probability of malignancy in an HCN, and patients should be counseled accordingly.

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Analytical Performance Verification of a Molecular Diagnostic for Cytology-Indeterminate Thyroid Nodules

Abstract: Analytical sensitivity, analytical specificity, robustness, and quality control of the GEC were successfully verified, indicating its suitability for clinical use.

Cited by 57 publications

References 15 publications

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane

Molecular markers in the diagnosis of thyroid nodules

Performance of the Afirma Gene Expression Classifier in Hürthle Cell Thyroid Nodules Differs from Other Indeterminate Thyroid Nodules

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