通过 ThyroSeq v2 下一代测序检测，对甲状腺结节滤泡性肿瘤/滤泡性肿瘤细胞学不典型的患者进行高度准确的癌症诊断。
Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.
机构信息
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
出版信息
Cancer. 2014 Dec 1;120(23):3627-34. doi: 10.1002/cncr.29038. Epub 2014 Sep 10.
BACKGROUND
Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules.
METHODS
The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples.
RESULTS
In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor γ (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%).
CONCLUSIONS
The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.
背景
细针穿刺细胞学检查（FNA）是评估甲状腺结节的常用方法，尽管 20%至 30%的 FNA 具有不确定的细胞学结果，这阻碍了对这些患者的适当管理。滤泡（或嗜酸细胞）肿瘤/疑似滤泡（或嗜酸细胞）肿瘤（FN/SFN）是一种常见的不确定诊断，癌症风险约为 15%至 30%。在这项研究中，作者测试了最完整的下一代测序（NGS）基因标记面板是否可以显著提高这些结节的癌症诊断率。
方法
评估了 143 例来自已知手术结果的患者的具有 FN/SFN 细胞学诊断的连续 FNA 样本，其中包括 91 例回顾性样本和 52 例前瞻性样本。使用专有的测序仪对 13 个基因的点突变和甲状腺癌中发生的 42 种基因融合进行了分析。使用 8 个基因的表达来评估 FNA 样本的细胞组成。
结果
在整个队列中，组织学分析显示 104 个良性结节和 39 个恶性结节。最常见的点突变涉及神经母细胞瘤 RAS 病毒癌基因同源物（NRAS），其次是 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）、端粒酶逆转录酶（TERT）基因和促甲状腺激素受体（TSHR）基因。鉴定的融合涉及甲状腺腺瘤相关（THADA）基因；过氧化物酶体增殖物激活受体γ（PPARG）基因；和神经营养酪氨酸激酶，受体，类型 3（NTRK3）基因。回顾性和前瞻性组的性能特征相似。在所有 FN/SFN 结节中，术前 ThyroSeq v2 的检测灵敏度为 90%（95%置信区间[CI]，80%-99%），特异性为 93%（95%CI，88%-98%），阳性预测值为 83%（95%CI，72%-95%），阴性预测值为 96%（95%CI，92%-100%），准确率为 92%（95%CI，88%-97%）。
结论
目前的结果表明，使用广泛的 NGS 面板对甲状腺结节进行综合基因分型可为 FN/SFN 细胞学的结节提供高度准确的诊断，并应有助于这些患者的最佳管理。
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