Molecular Profiling of Thyroid Nodules: Current Role for the Afirma Gene Expression Classifier on Clinical Decision Making

Kloos, Richard T.

doi:10.4274/2017.26.suppl.05

Cited by 44 publications

(60 citation statements)

References 83 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%

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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%

“…The Afirma GEC is a commonly used molecular test for indeterminate thyroid proliferations . The Afirma GEC uses a microarray device to measure the activity of over 100 genes.…”

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

confidence: 99%

Ancillary molecular testing of indeterminate thyroid nodules

Rossi

Larocca

Pantanowitz

2018

Cancer Cytopathology

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“…7-10 RAS mutations, the most common type in thyroid nodules, have been reported to have variable positive and negative predictive value for malignancy, often occurring in benign nodules. [18][19][20] A messenger RNA risk classifier can help to rule out the need for surgery in indeterminate nodules due to its high negative predictive value for malignancy. 16,17 Multiple studies have described the ability of RNA-based risk classifiers to help resolve diagnostic uncertainty in indeterminate thyroid nodules.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14][15] Furthermore, residual risk of malignancy (5%-25%) is present in patients who lack any detectable mutational change. 19,20 However, its less than optimal positive predictive value limits the ability to rule in the need for surgery, especially in AUS/FLUS nodules, where malignancy rates are low. [18][19][20] A messenger RNA risk classifier can help to rule out the need for surgery in indeterminate nodules due to its high negative predictive value for malignancy.…”

Section: Introductionmentioning

confidence: 99%

“…16,17 Multiple studies have described the ability of RNA-based risk classifiers to help resolve diagnostic uncertainty in indeterminate thyroid nodules. [19][20][21] Comparatively, non-coding microRNA based risk classifiers have shown similarly high negative predictive value (NPV) for malignancy and superior positive predictive value when used in combination with analysis for oncogenic mutations and messenger RNA fusion transcripts. 19,20 However, its less than optimal positive predictive value limits the ability to rule in the need for surgery, especially in AUS/FLUS nodules, where malignancy rates are low.…”

Section: Introductionmentioning

confidence: 99%

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Clinical impact of testing for mutations and microRNAs in thyroid nodules

Sistrunk

Shifrin

Frager

et al. 2019

Diagnostic Cytopathology

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Background We report results of a multicenter clinical experience study examining the likelihood of patients with indeterminate thyroid nodules to undergo surgery or have malignant outcome based on multiplatform combination mutation and microRNA testing (MPT). Methods MPT assessed mutations in BRAF, HRAS, KRAS, NRAS, and PIK3CA genes, PAX8/PPARγ, RET/PTC1, and RET/PTC3 gene rearrangements, and the expression of 10 microRNAs. Baseline clinical information at the time of MPT and clinical follow‐up records were reviewed for 337 patients, of which 80% had negative MPT results. Kaplan Meier analysis for cumulative probability of survival without having a surgical procedure or malignant diagnosis over the course of patient follow‐up was determined for MPT results of 180 patients, among which only 14% had malignancy. Results A negative MPT result in nodules with Bethesda III or IV cytology (2009) conferred a high probability of non‐surgical treatment, with only 11% expected to undergo surgery and a high probability of survival without malignancy (92%) for up to 2 years follow up. A positive MPT result conferred a 57% probability of malignancy and was an independent risk factor for undergoing surgical treatment (Hazard Ratio [HR] 9.2, 95% confidence intervals 5.4‐15.9, P < .0001) and for malignancy (HR 13.4, 95% confidence intervals 4.8‐37.2, P < .0001). For nodules with weak driver mutations, positive microRNA test results supported high risk of cancer while negative results downgraded cancer risk. Conclusion MPT results are predictive of real‐world decisions to surgically treat indeterminate thyroid nodules, with those decisions being appropriately aligned with a patient's risk of malignancy over time.

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Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules

et al. 2021

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IMPORTANCE Approximately 20% of thyroid nodules display indeterminate cytology. Molecular testing can refine the risk of malignancy and reduce the need for diagnostic hemithyroidectomy.OBJECTIVE To compare the diagnostic performance between an RNA test (Afirma genomic sequencing classifier) and DNA-RNA test (ThyroSeq v3 multigene genomic classifier). DESIGN, SETTING, AND PARTICIPANTSThis parallel randomized clinical trial of monthly block randomization included patients in the UCLA Health system who underwent thyroid biopsy from August 2017 to January 2020 with indeterminate cytology (Bethesda System for Reporting Thyroid Cytopathology category III or IV). INTERVENTIONS Molecular testing with the RNA test or DNA-RNA test. MAIN OUTCOMES AND MEASURES Diagnostic test performance of the RNA test compared with the DNA-RNA test. The secondary outcome was comparison of test performance with prior versions of the molecular tests. RESULTS Of 2368 patients, 397 were eligible for inclusion based on indeterminate cytology, and 346 (median [interquartile range] age, 55 [44-67] years; 266 [76.9%] women) were randomized to 1 of the 2 tests. In the total cohort assessed for eligibility, 3140 thyroid nodules were assessed, and 427 (13.6%) nodules were cytologically indeterminate. The prevalence of malignancy was 20% among indeterminate nodules. The benign call rate was 53% (95% CI, 47%-61%) for the RNA test and 61% (95% CI, 53%-68%) for the DNA-RNA test. The specificities of the RNA test and DNA-RNA test were 80% (95% CI, 72%-86%) and 85% (95% CI, 77%-91%), respectively (P = .33); the positive predictive values (PPV) of the RNA test and DNA-RNA test were 53% (95% CI, 40%-67%) and 63% (95% CI, 48%-77%), respectively (P = .33). The RNA test exhibited a higher PPV compared with the prior test version (Afirma gene expression classifier) (54% [95% CI, 40%-67%] vs 38% [95% CI, 27%-48%]; P = .01). The DNA-RNA test had no statistically significant difference in PPV compared with its prior version (ThyroSeq v2 next-generation sequencing) (63% [95% CI, 48%-77%] vs 58% [95% CI, 43%-73%]; P = .75). Diagnostic thyroidectomy was avoided in 87 (51%) patients tested with the RNA test and 83 (49%) patients tested with the DNA-RNA test. Surveillance ultrasonography was available for 90 nodules, of which 85 (94%) remained stable over a median of 12 months follow-up.CONCLUSIONS AND RELEVANCE Both the RNA test and DNA-RNA test displayed high specificity and allowed 49% of patients with indeterminate nodules to avoid diagnostic surgery. Although previous trials demonstrated that the prior version of the DNA-RNA test was more specific than the prior version of the RNA test, the current molecular test techniques have no statistically significant difference in performance.

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Molecular Profiling of Thyroid Nodules: Current Role for the Afirma Gene Expression Classifier on Clinical Decision Making

Cited by 44 publications

References 83 publications

Ancillary molecular testing of indeterminate thyroid nodules

Ancillary molecular testing of indeterminate thyroid nodules

Clinical impact of testing for mutations and microRNAs in thyroid nodules

Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules

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