Intronic RAS and PI3KCA mutations identified by Next Generation Sequencing in thyroid nodules with indeterminate cytology may associate with follicular thyroid cancer

Context.— Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. Objective.— To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material. Design.— A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes. Results.— Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses. Conclusions.— Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.

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Facilitating rapid precision oncology in anaplastic thyroid cancer: Clinical implications of next generation sequencing (NGS) mutation testing and impact on survival.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.6023 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 6023-6023 ◽

Cited By ~ 2

Author(s):

Jennifer Rui Wang ◽

Gilbert J Cote ◽

Mark Zafereo ◽

Priyanka C. Iyer ◽

Ramona Dadu ◽

...

Keyword(s):

Thyroid Cancer ◽

Next Generation Sequencing ◽

Anaplastic Thyroid Cancer ◽

Mutation Testing ◽

Clinical Implications ◽

Precision Oncology ◽

Next Generation ◽

Impact On Survival ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

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Highly accurate NGS-based multi-gene testing in the diagnosis of thyroid nodules with indeterminate cytology.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13579 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13579-e13579

Author(s):

Yuntao Song ◽

Bin Zhang ◽

Tonghui Ma

Keyword(s):

Next Generation Sequencing ◽

Mutation Analysis ◽

Predictive Value ◽

Thyroid Nodules ◽

Braf V600e Mutation ◽

Braf V600e ◽

Gene Testing ◽

Indeterminate Cytology ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

e13579 Background: Thyroid nodules are highly prevalent, Fine-needle aspiration (FNA) is the standard pre-operative tool for diagnosis. However, some of the samples are classified as indeterminate, which leads to unnecessary surgery. BRAF V600E mutation is often used as a diagnostic marker for thyroid cancer, and it is highly specific for papillary thyroid carcinoma (PTC). But BRAF mutation is rarely occurred in thyroid nodules with indeterminate cytology. To diagnose the indeterminate thyroid nodules precisely, some NGS-based multi-gene testing panel has been developed and clinically used in America and Europe, but rare research was reported in China. In this study, we evaluated the value of a next-generation sequencing (NGS) panel to cancer diagnosis in indeterminate thyroid nodules. Methods: From February 2018 to September 2018, 360 patients with thyroid nodules who underwent FNA at Peking University Cancer Hospital were enrolled. And the FNA samples with indeterminate cytology were evaluated using a next-generation sequencing (NGS) assay, including 16 genes analyzed for point mutations and 26 types of gene fusions. Diagnostic performance of this multi-gene testing panel was compared with BRAF V600E single gene mutation analysis. Results: 141 nodules were cytologically indeterminate among 360 patients on FNA biopsy, 72 of which were resected and analyzed by NGS successfully. Histologic analysis after surgery revealed 41 (56.9%) cancers in these 72 patients. The multi-gene testing assay could classify 30/41 cancers correctly, showing a sensitivity of 73.2%, specificity of 96.8%, positive predictive value of 96.8%, and negative predictive value of 73.2%. The diagnostic accuracy of the multi-gene testing was significantly higher than the BRAF V600E mutation analysis (83.3% vs 73.6%, x2= 31.588, p < 0.01). Conclusions: Our study demonstrated that the multi-gene testing provided both high sensitivity and high specificity for cancer detection in thyroid nodules with indeterminate cytology, and its accuracy was much higher than BRAF V600E mutation test.

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