Risk Stratification Study of Indeterminate Thyroid Nodules with a next-generation Sequencing Assay with Residual ThinPrep® Material.
Risk Stratification Study of Indeterminate Thyroid Nodules with a next-generation Sequencing Assay with Residual ThinPrep® Material.
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DOI：
10.7150/jca.46086
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发表时间：
2020
影响因子：
3.9
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Zhao H;Jing W;Li W;Zhang Z;Cao J;Zhao L;Sun Y;Wang C;Wang Y;Guo H
目的：不确定性甲状腺结节的治疗具有挑战性。分子检测已成为细针穿刺（FNA）细胞学的灰色区域分层的一种有前途的方法。下一代测序（NGS）可用于测试大量的遗传变化与非常少量的核酸从FNA样品获得。研究方法：在常规ThinPrep®载玻片制备后，根据Bethesda甲状腺细胞病理学报告系统对甲状腺FNA测定进行分类。使用具有残余ThinPrep®材料的18基因NGS组分析具有手术结果的不确定结节，包括分类为未确定意义的结节（AUS）/未确定意义的滤泡性病变（FLUS）或滤泡性肿瘤（FN）/疑似滤泡性肿瘤（SFN）的结节。我们评估了18基因组对甲状腺恶性肿瘤和潜在恶性肿瘤的诊断功效，并将其与公认的检查ThyroSeq v2测试进行了比较。结果：共检测了36个不确定的结节，其中7个被归类为AUS/FLUS，29个被归类为FN/SFN。他们都有足够的DNA进行NGS程序。当具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤（NIFTP）被认为是恶性时，AUS/FLUS结节的恶性风险为71.4%，FN/SFN结节的恶性风险为69.0%。18个基因的面板显示72.0%的敏感性，72.7%的特异性，85.7%的阳性预测值（PPV），和53.3%的阴性预测值（NPV）在确定恶性肿瘤和潜在的恶性肿瘤在不确定的结节。与来自ThyroSeq v2测试的多中心报告相比，18基因组显示出较低的NPV（p=0.005），但较高的PPV（p=0.02）。结论：NGS测定法对残留ThinPrep®材料是可行的，其优点是不需要额外的FNA程序。18基因组测试可用作基于不确定结节的手术管理的“规则”测试，并且与ThyroSeq v2测试相比显示出较低的NPV但较高的PPV。
Objective: The management of indeterminate thyroid nodules is challenging. Molecular testing has emerged as a promising method for stratifying this gray area of fine-needle aspiration (FNA) cytology. Next-generation sequencing (NGS) can be used to test a large variety of genetic changes with very small amounts of nucleic acids obtained from FNA samples. Methods: Thyroid FNA assays were classified according to the Bethesda System for Reporting Thyroid Cytopathology after routine ThinPrep® slide preparation. Indeterminate nodules with surgical outcomes were assayed with an 18-gene NGS panel with the residual ThinPrep® material, including nodules categorized as atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN)/suspicious for a follicular neoplasm (SFN). We evaluated the diagnostic efficacy of the 18-gene panel for thyroid malignancies and potential malignancies and compared it with a well-accepted examination, ThyroSeq v2 testing. Results: A total of 36 indeterminate nodules were assayed, seven were categorized as AUS/FLUS and 29 as FN/SFN. All of them had adequate DNA for the NGS procedure. When noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was considered malignant, the risk of malignancy was 71.4% for AUS/FLUS nodules, and 69.0%for FN/SFN nodules. The 18-gene panel showed 72.0% sensitivity, 72.7% specificity, 85.7% positive predictive value (PPV), and 53.3% negative predictive value (NPV) in identifying malignancies and potential malignancies in the indeterminate nodules. Compared with a multicenter report from ThyroSeq v2 testing, 18-gene panel showed a lower NPV (p=0.005), but a higher PPV (p=0.02). Conclusions: NGS assays are feasible on residual ThinPrep® material, with the advantage of not requiring additional FNA procedure. The 18-gene panel testing can be used as a 'rule in' test for surgical management based on indeterminate nodules and showed a lower NPV but a higher PPV compared to ThyroSeq v2 testing.