DIAGNOSIS OF ENDOCRINE DISEASE: Usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer

Stewardson, Paul; Eszlinger, Markus; Paschke, Ralf

doi:10.1530/eje-21-1293

Cited by 12 publications

(10 citation statements)

References 95 publications

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“…Our gene signature technology can potentially be applied to fine needle aspirates (FNA) from thyroid nodules. Currently, commercially available genomic assays for thyroid nodule aspirates (such as ThyroSeq ( 42 ) and Thyrospec ( 43 )) focus on diagnosis and estimating the risk of malignancy, particularly in indeterminate cell samples (Bethesda 4). Another such test, Afirma ( 44 ), described as a genomic sequencing classifier, also detects gene variants (including BRAF V600E mutations) and fusions in nodules that are clearly malignant (Bethesda 6) or are suspicious for malignancy (Bethesda 5).…”

Section: Discussionmentioning

confidence: 99%

A clinically useful and biologically informative genomic classifier for papillary thyroid cancer

Craig,

Stretch,

Farshidfar

et al. 2023

Front. Endocrinol.

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Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm (HighLifeR) to 502 cases annotated by The Cancer Genome Atlas Project to derive an accurate molecular prognostic classifier. Unsupervised analysis of the 82 genes that were most closely associated with recurrence after surgery enabled the identification of three unique molecular subtypes. One subtype had a high recurrence rate, an immunosuppressed microenvironment, and enrichment of the EZH2-HOTAIR pathway. Two other unique molecular subtypes with a lower rate of recurrence were identified, including one subtype with a paucity of BRAFV600E mutations and a high rate of RAS mutations. The genomic risk classifier, in addition to tumor size and lymph node status, enabled effective prognostication that outperformed the American Thyroid Association clinical risk stratification. The genomic classifier we derived can potentially be applied preoperatively to direct clinical decision-making. Distinct biological features of molecular subtypes also have implications regarding sensitivity to radioactive iodine, EZH2 inhibitors, and immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 99%

A clinically useful and biologically informative genomic classifier for papillary thyroid cancer

Craig,

Stretch,

Farshidfar

et al. 2023

Front. Endocrinol.

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show abstract

“…Our gene signature technology can potentially be applied to fine needle aspirates (FNA) from thyroid nodules. Currently, commercially available genomic assays for thyroid nodule aspirates (such as ThyroSeq 43 and Thyrospec 44 ) focus on diagnosis and estimating the risk of malignancy, particularly in indeterminate cell samples (Bethesda 4). Another such test, Afirma 45 , described as a genomic sequencing classifier, also detects gene variants (including BRAF V600E mutations) and fusions in nodules that are clearly malignant (Bethesda 6) or are suspicious for malignancy (Bethesda 5).…”

Section: Discussionmentioning

confidence: 99%

A Clinically Useful and Biologically Informative Genomic Classifier for Papillary Thyroid Cancer

Craig

Stretch

Farshidfar

et al. 2022

Preprint

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Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm (HighLifeR) to 502 cases annotated by The Cancer Genome Atlas Project to derive an accurate molecular prognostic classifier. Unsupervised analysis of the 82 genes that were most closely associated with recurrence after surgery enabled identification of three unique molecular subtypes. One subtype had a high recurrence rate, an immunosuppressed microenvironment, and enrichment of the EZH2-HOTAIR pathway. Two other unique molecular subtypes with a lower rate of recurrence were identified, including one subtype with a paucity of BRAFV600E mutations and a high rate of RAS mutations. The genomic risk classifier, in addition to tumor size and lymph node status, enabled effective prognostication that outperformed the American Thyroid Association clinical risk stratification. The genomic classifier we derived can potentially be applied preoperatively to direct clinical decision-making. Distinct biological features of molecular subtypes also have implications regarding sensitivity to radioactive iodine, EZH2 inhibitors, and immune checkpoint inhibitors.

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“…20 It is crucial to audit the institutional quality and outcomes of each of these diagnostic steps before systematically implementing molecular tests. 20 In particular, the following factors need to be accounted for (Figure 1).…”

Section: Molecular Tests For the Evaluation Of Cytologically Indeterm...mentioning

confidence: 99%

“…Therefore, clinical, radiological and cytological information that precedes the molecular test needs to be considered for the indication and correct interpretation of the molecular test's results. Thus, the use of molecular tests for diagnostic purposes needs to be integrated into the evidence‐based institutional thyroid nodule evaluation pathway 20 . It is crucial to audit the institutional quality and outcomes of each of these diagnostic steps before systematically implementing molecular tests 20 .…”

Section: Molecular Tests For the Evaluation Of Cytologically Indeterm...mentioning

confidence: 99%

“…Thus, the use of molecular tests for diagnostic purposes needs to be integrated into the evidence‐based institutional thyroid nodule evaluation pathway 20 . It is crucial to audit the institutional quality and outcomes of each of these diagnostic steps before systematically implementing molecular tests 20 . In particular, the following factors need to be accounted for (Figure 1).…”

Section: Molecular Tests For the Evaluation Of Cytologically Indeterm...mentioning

confidence: 99%

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Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer

Valderrábano

Eszlinger

Stewardson

et al. 2023

Clinical Endocrinology

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Objective Advances in our understanding of the molecular biology of thyroid tumours is being rapidly translated into their clinical management. This review summarizes the current use of molecular testing in thyroid tumours, focusing on their usefulness as diagnostic and prognostic tools to guide treatment with consideration of present limitations. Design Considerations about molecular testing applications for the diagnosis and treatment of thyroid tumours are divided into four sections/roles: (1) evaluating cytologically indeterminate thyroid nodules; (2) guiding extent of surgery in indeterminate thyroid nodules; (3) completing histological characterization of thyroid tumours and (4) identifying actionable mutations in advanced progressive thyroid cancers. Results Genomic testing can improve the presurgical malignancy risk assessment in indeterminate thyroid nodules. However, a prior in‐depth analysis of institutional quality and outcomes of sonographical, cytological and histological characterization of thyroid tumours is necessary. Presently, it remains uncertain whether knowing the molecular profile of a cytologically indeterminate thyroid nodule might be advantageous to modify the extent of initial surgery. Molecular characterization of thyroid tumours can be a valuable adjunct to morphological diagnosis in some challenging cases, such as in low‐risk follicular cell‐derived neoplasms, or rare tumours. Finally, as selective kinase inhibitors are available, molecular testing in locally advanced/metastatic progressive thyroid cancers should also be integrated into the institutional clinical management pathway to improve outcomes and limit toxicity. Conclusions Molecular testing needs to be implemented into the local evidence‐based clinical management thyroid nodule/cancer pathways to improve its diagnostic and prognostic value and to optimize cost‐effectiveness.

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DIAGNOSIS OF ENDOCRINE DISEASE: Usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer

Cited by 12 publications

References 95 publications

A clinically useful and biologically informative genomic classifier for papillary thyroid cancer

A clinically useful and biologically informative genomic classifier for papillary thyroid cancer

A Clinically Useful and Biologically Informative Genomic Classifier for Papillary Thyroid Cancer

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer

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