Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China

Song, Yuntao; Xu, Gaixia; Ma, Tianzhou; Zhu, Yanli; Yu, Hao; Yu, Wenbin; Wei, Wei; Wang, Tianxiao; Zhang, Bin

doi:10.1002/cam4.3450

Cited by 14 publications

(17 citation statements)

References 34 publications

(62 reference statements)

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“…In the literature, Nikiforov et al also reported that only one of three TSHR mutation-positive nodules was identified as cancer after surgery and two NRAS -mutated samples were benign on histology ( 30 ). Furthermore, RAS mutations are considered to be not specifically associated with malignant (75–88%) or potentially malignant outcomes ( 7 , 27 , 31 , 32 , 33 ) and are highly predictive of predominantly low-risk follicular-pattern carcinomas ( 34 ), which is further supported by our results of a significantly lower frequency of lymph node metastasis in RAS -mutated malignancies. Additional gene mutations including SPOP , EZH1 , and ZNF148 are also suggested to be benign markers ( 32 ).…”

Section: Discussionsupporting

confidence: 80%

“…Furthermore, RAS mutations are considered to be not specifically associated with malignant (75–88%) or potentially malignant outcomes ( 7 , 27 , 31 , 32 , 33 ) and are highly predictive of predominantly low-risk follicular-pattern carcinomas ( 34 ), which is further supported by our results of a significantly lower frequency of lymph node metastasis in RAS -mutated malignancies. Additional gene mutations including SPOP , EZH1 , and ZNF148 are also suggested to be benign markers ( 32 ). Therefore, additional features are needed for a more accurate malignancy prediction in thyroid nodules with TSHR , NRAS , or some ‘low-risk’ gene mutations.…”

Section: Discussionsupporting

confidence: 80%

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Diagnostic performance of next-generation sequencing and genetic profiling in thyroid nodules from a single center in China

Ren

Yao

Bao

et al. 2022

European Thyroid Journal

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Objective: The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules. Methods: A total of 1039 FNA and surgical resection samples tested using the targeted multigene NGS panel were retrospectively collected. The features of gene alterations in different thyroid tumors were analyzed, and the diagnostic efficacy were evaluated. Results: Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of 3 follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA-RNA based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sensitivity and specificity of NGS testing were 79.2% (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively. Conclusions: Our study revealed the distinct molecular profile of thyroid tumors in Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 80%

Diagnostic performance of next-generation sequencing and genetic profiling in thyroid nodules from a single center in China

Ren

Yao

Bao

et al. 2022

European Thyroid Journal

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“…Below, two of these latter studies that focused on the clinical output of the custom panels along with their analytical performance are discussed in detail [19,23]. Song et al designed a custom NGS panel, the FSZ-Thyroid NGS panel, covering at least 1000 hotspots in 16 thyroid-cancer-related genes, including the AKT1, BRAF, CTNNB1, EIF1AX, EZH1, GNAS, HRAS, KRAS, NRAS, PIK3CA, RET, SPOP, TERT, TP53, TSHR and ZNF148 genes.…”

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

confidence: 99%

“…Song et al designed a custom NGS panel, the FSZ-Thyroid NGS panel, covering at least 1000 hotspots in 16 thyroid-cancer-related genes, including the AKT1, BRAF, CTNNB1, EIF1AX, EZH1, GNAS, HRAS, KRAS, NRAS, PIK3CA, RET, SPOP, TERT, TP53, TSHR and ZNF148 genes. This panel was adopted to process a prospective series of 196 indeterminate FNAs (153 AUS/FLUS and 43 FN/SFN) [23]. High-quality nucleic acids were extracted from cells obtained by a dedicated pass.…”

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

confidence: 99%

“…The authors obtained, among the indeterminate Bethesda FNAs, a sensitivity of 73%, specificity of 80%, PPV of 71% and NPV of 82%, by considering the low-risk neoplasms, such as non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFT-P) and follicular and well-differentiated tumors of uncertain malignant potential (FT-UMP) as benign nodules. Although one of the strengths of this series is its prospective approach, the indications for surgery were given not only on the basis of cytological and molecular features of the nodules but also taking into account their clinical and US appearances [23].…”

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

confidence: 99%

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

Bellevicine¹,

Sgariglia²,

Nacchio³

et al. 2021

JMP

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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.

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Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules

Yang,

Nga,

Bundele

et al. 2024

Cancer Cytopathology

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BackgroundMost thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine‐needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy.MethodsThis prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex‐vivo FNA samples. Centralized pathology review also was performed.ResultsOf 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III–IV cytology nodules. Most positive samples had RAS‐like (41.7%), followed by BRAF‐like (22.6%), and high‐risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS‐like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF‐like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high‐suspicion ultrasound characteristics according to American Thyroid Association criteria.ConclusionsEven in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III–IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

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Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 34 publications

Diagnostic performance of next-generation sequencing and genetic profiling in thyroid nodules from a single center in China

Diagnostic performance of next-generation sequencing and genetic profiling in thyroid nodules from a single center in China

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

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules

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