Centralized Molecular Testing for Oncogenic Gene Mutations Complements the Local Cytopathologic Diagnosis of Thyroid Nodules

Beaudenon‐Huibregtse, Sylvie; Ek, Alexander; Rb, Guttler; Jm, Hershman; Babu,; Tc, Blevins; Moore, Pamela B.; Andruss, Bernard F.; Labourier, Emmanuel

doi:10.1089/thy.2013.0640

Cited by 121 publications

(119 citation statements)

References 35 publications

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“…Because the original study of the seven-gene oncogene panel in which a posttest PoM of 6% for Bethesda III mutation-negative specimens was reported (16), observation has been considered acceptable in this subgroup of patients (7). However, our results, in agreement with a more recent, multicenter, blinded study using this panel, show a lower NPV that would made observation inappropriate in this setting (9). Between July 2012 and January 2014, miRInform was used sporadically at our institution.…”

Section: Discussionsupporting

confidence: 89%

“…It is important to note that these predictive values are calculated with the estimated sensitivity and specificity of single studies, each of them with limited sample size and wide confidence intervals, which could differ significantly from the true performance. This might be especially relevant in the calculations made for ThyroSeq v2 because the test metrics used for these calculations are derived from a single institution, nonblinded study, whereas for Afirma and miRInform, these parameters are derived from multicenter and blinded studies (8,9,10,11). For example, the original single-center, nonblinded study of the sevengene oncogene panel (upon which miRInform was based) performed rather better than in the more recent multicenter, blinded study, emphasizing the fact that singlecenter results lack external validation (9,16).…”

Section: Discussionmentioning

confidence: 99%

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Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

Valderrábano¹,

Leon

Centeno

et al. 2016

European Journal of Endocrinology

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Objective: Several molecular marker tests are available to refine the diagnosis of thyroid nodules. Knowing the true prevalence of malignancy (PoM) within each cytological category is considered necessary to select the most appropriate test and to interpret results accurately. We describe our institutional PoM among cytological categories and report our experience with molecular markers. Design: Single-center retrospective study. Methods: We calculated the institutional PoM for each category of the Bethesda system (Bethesda) on all thyroid nodules with cytological evaluation from October 2008 to May 2014. We estimated the predictive values for Afirma, miRInform, and ThyroSeq v2, based on published sensitivity and specificity. Finally, we assessed our own experience with miRInform. Results: The PoMs for Bethesda III and IV categories were 21 and 28%, respectively. ThyroSeq v2 achieves the highest theoretical negative and positive predictive values (NPV and PPV) in Bethesda III (98 and 75%) and Bethesda IV categories (96 and 83%). At our institution, miRInform detected a mutation in 16% of 109 indeterminate nodules tested, all in Bethesda IV specimens. Histology was available in 56 (51%) nodules. The observed sensitivity and specificity in Bethesda IV specimens were 63 and 86%, yielding an NPV and a PPV of 75 and 77%, respectively. Conclusions: For our current Bethesda III and IV PoM, the actual performance of miRInform was worse than expected. Theoretically ThyroSeq v2 should have the best performance, but it could be affected in the same way as miRInform, given the similarities between the tests. Assessing the institutional performance of each test is necessary along with PoM individualization.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

Valderrábano¹,

Leon

Centeno

et al. 2016

European Journal of Endocrinology

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“…A subsequent prospective single-institution study of 513 surgically resected thyroid nodules with indeterminate cytologic diagnosis showed that if any of the above gene mutations or fusions were identified, the PPV was 88% and 87% for AUS/FLUS and FN/SFN, respectively. 37 The high PPV of the gene mutation test is similar to the values obtained in other similar studies 38,39 and indicates that the ThyroSeq test could potentially be used as a ''rule in'' test.…”

Section: Afirma Gene Expression Classifiersupporting

confidence: 80%

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

164

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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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“…Similarly, molecular mutation analyses in cystic neoplasia of the pancreas and of thyroid lesions of indeterminate cytology can be used to help differentiate benign from malignant lesions [16][17][18][19][20][21][22][23][24][25] . In suspected Stratification of cancer has now become a part of the primary diagnosis.…”

Section: Importance Of Molecular Diagnosis In Oncologymentioning

confidence: 99%

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

Joseph

Cankovic

Caughron³

et al. 2016

The Journal of Molecular Diagnostics

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Centralized Molecular Testing for Oncogenic Gene Mutations Complements the Local Cytopathologic Diagnosis of Thyroid Nodules

Cited by 121 publications

References 35 publications

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

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

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer

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