Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States

Nishino, Michiya; Bellevicine, Claudio; Baloch, Zubair W.

doi:10.3390/jmp2020014

Cited by 12 publications

(11 citation statements)

References 68 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the moment, four molecular tests are commercially available in the USA to diagnose and evaluate RR for TCs. Principally, each single test is able to detect BRAF as well as molecular alterations of RET on FNA samples [18,34]. Despite this, partial information is available on the effectiveness of molecular tests for cytopathology diagnosis of TCs.…”

Section: Epidemiological Monitoring Valid Bms and New Proposals For Tcsmentioning

confidence: 99%

See 1 more Smart Citation

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers

Trovato

2022

Diagnostics

View full text Add to dashboard Cite

Biomarkers (BMs) are medical signs which can be precisely measured and reproduced. Mainly, BMs provide information on the likely disease which can occur in an individual. On the other hand, BMs also signal disease recurrence in patients receiving therapy. The U.S. Food and Drug Administration coupled with the National Institutes of Health and the European Medicines Agency have proposed two distinct procedures to validate BMs. These agencies have elaborated two glossaries to describe the role of BMs. The aim of this study was to investigate medical taxonomies adopted by different governmental agencies for BM validation. Additional goals were to analyze efficiencies of the validated and candidate BMs for thyroid cancers (TCs). Currently, thyroglobulin is validated for monitoring TCs. Sorafenib-tosylate, Doxorubicin-hydrochloride, Vandetanib, Cabozantinib-s-malate, Dabrafenib-mesylate, Trametinib-dimethyl-sulfoxide, Lenvatinib-mesylate, Pralsetinib and Selpercatinib are validated for TC treatment. Among candidate BMs for TC diagnosis, there are molecular combinations including BRAF, RAS, RET/PTC and PAX8-PPARγ mutations. Noteworthy are BRAF and RET/PTC alterations already validated as targets of Dabrafenib-mesylate, Pralsetinib and Selpercatinib. Finally, cellular expressions of c-met in nodal TC metastases have diagnostic imaging applications. On the basis of this analysis, BM taxonomies should have common standards internationally recognized. BMs show different efficiencies depending on their diagnostic or therapeutic use.

show abstract

Section: Epidemiological Monitoring Valid Bms and New Proposals For Tcsmentioning

confidence: 99%

“…To date, histological classification of TC variants remains the best BM for diagnosis and prognosis of thyroid malignancies [15,16]. However, numerous molecules have been proposed as adequate diagnostic and risk BMs for TCs in recent times [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers

Trovato

2022

Diagnostics

View full text Add to dashboard Cite

show abstract

“…After the introduction of the next-generation sequencing (NGS) platforms, testing strategies have moved away from the traditional method, which allows the sequencing of a limited number of genes, in favor of massive parallel sequencing. However, the custom NGS panels specifically developed to comprehensively cover thyroid-specific genomic alterations by centralized laboratories are proprietary and not commercially available or locally employable (e.g., Thyroseq) [7]. Conversely, cancer-generic NGS panels, featuring the most common genomic alterations found in solid tumors, represent a possible solution for the processing of cytological samples.…”

Section: From Single Gene Testing To Parallel and Massive Sequencing Analysismentioning

confidence: 99%

“…The choice of the "ideal" molecular test is also influenced by the local prevalence of thyroid neoplasms and the resulting difference in malignancy rates in each TBSRTC category [3,6]. These advances and comprehensive thyroid-specific commercially available tests are centralized in North America private laboratories; in countries with universal healthcare system coverage like in Europe, the access to such advanced molecular tests can be prohibitive because of its very high cost and lack of reimbursement policies [7] As an alternative to thyroid-specific comprehensive testing, several centers have introduced sustainable solutions based on either the adoption of commercially available generic cancer panels not specifically designed for thyroid samples or the design and validation of narrow custom panels targeting the most relevant genomic alterations involved in thyroid carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Molecular Testing of Thyroid Fine-Needle Aspiration: Local Issues and Solutions. An Interventional Cytopathologist Perspective

Bellevicine¹,

Sgariglia²,

Nacchio³

et al. 2021

JMP

Self Cite

View full text Add to dashboard Cite

Molecular testing has acquired a relevant role for diagnostic and prognostic stratification of indeterminate thyroid nodules. Besides the available commercial solutions marketed in the United States, various local testing strategies have been developed in the last decade. In this setting, the modern interventional cytopathologist, the physician who performs the both aspirate and the morphologic interpretation plays a key role in the correct handling of fine-needle aspiration (FNA) samples not only for microscopy but also for molecular techniques. This review summarizes experiences with local approaches to the molecular testing of thyroid FNA, highlighting the role of the modern interventional cytopathologist.

show abstract

“…These now conventional predictive markers for thyroid cancer are based on genotypes, and the predictive abilities of these tests are variable and highly dependent on regional differentiated thyroid cancer (DTC) prevalence and genetic signatures (4,5). In the United States, three main types of molecular tests have been commercially developed over the past decade for cytologically undetermined thyroid nodules: ThyroSeq v3 (University of Pittsburgh Medical Centre and Sonic Healthcare, USA); ThyGeNEXT and ThyraMIR (Interpace Diagnostics, USA); and Afirma Gene Sequencing Classifier (GSC) and Xpression Atlas (Veracyte, USA), with sensitivities of 94%, 93%, and 91% and specificities of 82%, 62%, and 68%, respectively (10). Despite the great sensitivities, the assays lack specificity, causing concern in endocrinologists and patients alike in light of many operations performed for what appeared to be suspicious lesions but proven to be benign after all (11).…”

Section: Introductionmentioning

confidence: 99%

Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers

et al. 2022

View full text Add to dashboard Cite

BackgroundThyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3+CD4-CD8-), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells’ proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy.MethodsWe recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves’ disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3+CD4-CD8- (DN T) as a function of total CD3+ cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings.ResultsThe DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3+ cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915–1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures.ConclusionThe present study proposes DN T cells’ proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation.

show abstract

Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States

Cited by 12 publications

References 68 publications

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers

Molecular Testing of Thyroid Fine-Needle Aspiration: Local Issues and Solutions. An Interventional Cytopathologist Perspective

Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers

Contact Info

Product

Resources

About