Impact of Molecular Screening for Point Mutations and Rearrangements in Routine Air-Dried Fine-Needle Aspiration Samples of Thyroid Nodules

Eszlinger, Markus; Krogdahl, Annelise; Münz, S.; Rehfeld, Christian; Jensen, Eva Magrethe Precht; Ferraz, Carolina; Bösenberg, Eileen; Drieschner, Norbert; Scholz, Markus; Hegedűs, László; Paschke, Ralf

doi:10.1089/thy.2013.0278

Cited by 93 publications

(101 citation statements)

References 32 publications

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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

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 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

158

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“…Recently, Labourier et al (2015) reported that the use of multiplatform testing in the clinical setting could potentially result in a 6-7-fold reduction in the number of unnecessary surgeries, thanking to its high negative predictive value in cytological indeterminate thyroid nodules (BSRTC categories III-V). This finding seems to be in contrast to the previous observation that the BRAF mutation seems to be less important in follicular neoplasms (Eszlinger et al, 2014). In our study, the BRAF V600E mutation, the most frequent mutation in thyroid cancer, was found only in the Thy 3a category.…”

Section: Discussioncontrasting

confidence: 99%

Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes

Giusti¹,

Massa²,

Balestra³

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:The cytology of 130 indeterminate nodules (Thy 3) was retrospectively reviewed according to the British Thyroid Association 2014 classification. Nodules were divided into Thy 3a (atypical features) and Thy 3f (follicular lesion) categories. Histology was available as a reference for 97 nodules. Pre-surgical evaluations comprised biochemical tests, color-Doppler ultrasonography (US), semi-quantitative elastography-US (USE), contrast-enhanced US (CEUS), and mutation analysis from cytological slides. Thyroid malignancy was the final diagnosis for 19% of surgicallytreated nodules. No statistically significant difference in the risk of malignancy was found between Thy 3a (26%) and Thy 3f (14%) nodules. Histology of the Thy 3a and Thy 3f nodules showed a higher incidence of Hurtle cell adenomas in Thy 3f (29%) than in Thy 3a (3%) nodules (P=0.01). The only pre-surgical difference concerned the BRAF V600E mutation, which was positive in some Thy 3a but not in any Thy 3f nodules (P=0.04). Receiver-operating characteristic (ROC) analysis was used to obtain cut-off values from US (score), USE (ELX 2/1 strain index), and CEUS (time-topeak index and peak index) data. The cut-off values were similar for Thy 3a and Thy 3f nodules. Data showed that malignancy can be suspected if the US score is >2, ELX 1/2 strain index >1, time-to-peak index >1, and peak index <1. In a sub-group of 24 revised nodules (12 Thy 3a and 12 Thy 3f) with histology as a reference, the diagnostic power of cumulative pre-surgical analysis by means of US, USE, and CEUS showed high positive and negative predictive values (83% and 100%, respectively) for the presence of malignancy in Thy 3a and Thy 3f nodules. In conclusion, in our series of revised Thy 3 nodules, malignancy was low and displayed no significant differences between Thy 3a and Thy 3f categories. The use of cut-offs based on histology as a reference could reduce surgery. Our data support the conviction that, in mutation-negative Thy 3a and Thy 3f nodules, observation should be the first choice when not all instrumental results are suspect.

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“…This point needs to be considered when other sources of samples such as cell block or cytology preparation with preserving liquid are used and specific protocols have to be applied in order to obtain high-quality nucleic acid isolation [16] Different types of specimen obtained from thyroid FNA procedure may be used for molecular analysis: (a) cells collected from FNA during the procedure [11], (b) cells retrieved from FNA-stained smears [1], (c) cells retrieved from air-dried slides [17], and (d) paraffin sections from cell blocks. All these samples have been shown to be suitable for point mutation analysis as well as for detecting chromosome rearrangements [17]. The different assays should be optimized for small size specimens and validated for the different cytology specimens.…”

Section: Introduction/backgroundmentioning

confidence: 99%

“…Nucleic acid recovering from direct smears offers relevant advantages: first, it permits to check the cells before nucleic acid isolation, allowing the analysis of exactly those cells that are cytologically indeterminate and the enrichment of the pathological population [16, 17]. This is not possible if a dedicated pass of FNA is washed in a tube containing nucleic acid preservative solution.…”

Section: Introduction/backgroundmentioning

confidence: 99%

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

Paschke¹,

Cantara²,

Crescenzi³

et al. 2017

Eur Thyroid J

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125

127

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Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

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Impact of Molecular Screening for Point Mutations and Rearrangements in Routine Air-Dried Fine-Needle Aspiration Samples of Thyroid Nodules

Cited by 93 publications

References 32 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

Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

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