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Background: Most 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.

Methods: This 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.

Results: Of 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.

Conclusions: Even 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.

Titel:	Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.
Autor/in / Beteiligte Person:	Yang, SP ; Nga, ME ; Bundele, MM ; Chiosea, SI ; Tan, SH ; Lum, JHY ; Parameswaran, R ; Lim, MY ; Li, H ; Cheah, WK ; Sek, KS ; Tan, ATH ; Loh, TKS ; Ngiam, KY ; Tan, WB ; Huang, X ; Ho, TWT ; Lim, KH ; Lim, CM ; Singaporewalla, RM ; Rao, AD ; Rao, NCL ; Chua, DYK ; Chin, DC ; Wald, AI ; LiVolsi, VA ; Nikiforov, YE ; Tai, ES
Link:	Full Text Finder (Volltext)
Zeitschrift:	Cancer cytopathology, Jg. 132 (2024-05-01), Heft 5, S. 309-319
Veröffentlichung:	Hoboken, NJ : Wiley-Blackwell, 2024
Medientyp:	academicJournal
ISSN:	1934-6638 (electronic)
DOI:	10.1002/cncy.22796
Schlagwort:	Humans Female Male Biopsy, Fine-Needle Middle Aged Prospective Studies Adult Aged Thyroid Neoplasms genetics Thyroid Neoplasms pathology Thyroid Neoplasms diagnosis Genomics methods Mutation Biomarkers, Tumor genetics Young Adult Asia, Southeastern Prognosis Aged, 80 and over Southeast Asian People Thyroid Nodule genetics Thyroid Nodule pathology Thyroid Nodule diagnosis
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't Language: English [Cancer Cytopathol] 2024 May; Vol. 132 (5), pp. 309-319. <i>Date of Electronic Publication: </i>2024 Feb 06. MeSH Terms: Thyroid Nodule* / genetics ; Thyroid Nodule* / pathology ; Thyroid Nodule* / diagnosis ; Humans ; Female ; Male ; Biopsy, Fine-Needle ; Middle Aged ; Prospective Studies ; Adult ; Aged ; Thyroid Neoplasms / genetics ; Thyroid Neoplasms / pathology ; Thyroid Neoplasms / diagnosis ; Genomics / methods ; Mutation ; Biomarkers, Tumor / genetics ; Young Adult ; Asia, Southeastern ; Prognosis ; Aged, 80 and over ; Southeast Asian People References: Dean DS, Gharib H. Epidemiology of thyroid nodules. Best Pract Res Clin Endocrinol Metabol. 2008;22(6):901‐911. doi:10.1016/j.beem.2008.09.019. ; Guth S, Theune U, Aberle J, Galach A, Bamberger CM. 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Molecular testing for cytologically suspicious and malignant (Bethesda V and VI) thyroid nodules to optimize the extent of surgical intervention: a retrospective chart review. J Otolaryngol Head Neck Surg. 2021;50(1):29. doi:10.1186/s40463‐021‐00500‐6. Grant Information: Endocrine and Metabolic Society of Singapore; National University Healthcare System Clinician Scientist Program Contributed Indexing: Keywords: ThyroSeq; clinical utility; clinical validation; thyroid cancer prediction; thyroid cancer prognostication; thyroid molecular test Substance Nomenclature: 0 (Biomarkers, Tumor) Entry Date(s): Date Created: 20240206 Date Completed: 20240501 Latest Revision: 20240501 Update Code: 20240501

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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.