Diagnostic Genetics, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Cytopathol. 2019 Mar;127(3):146-160. doi: 10.1002/cncy.22098. Epub 2019 Jan 8.
Molecular testing is recommended as an adjunct to improve the preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. Centrifuged supernatants from FNA samples, which are typically discarded, have recently emerged as a novel liquid-based biopsy for molecular testing. This study evaluates the use of thyroid FNA supernatants for detecting clinically relevant mutations.
Supernatants from thyroid FNA samples (n = 156) were evaluated. A 50-gene next-generation sequencing (NGS) assay was used, and mutation analysis results from a subset of samples were further compared with those of paired FNA smears and/or cell blocks.
All 156 samples yielded adequate DNA (median, 135 ng; range, 11-3180 ng), and 129 of these samples (83%) were successfully sequenced by NGS. The most frequently detected somatic mutations included BRAF and RAS mutations, which were followed by RET, TP53, PTEN, CDKN2A, and PIK3CA mutations. Eleven of 31 cases with an indeterminate cytologic diagnosis and 9 of 12 cases that were suspicious for malignancy had somatic mutations, including the BRAF V600E mutation, which is highly definitive for papillary thyroid carcinoma (PTC). Seven of the 9 indeterminate and suspicious cases with the BRAF V600E mutation had surgical follow-up, and they were all confirmed to be PTC. A comparison of the mutation profiles derived from supernatants with those of paired smears and/or cell blocks in a small subset of cases (n = 8) showed 100% concordance.
This study provides evidence that FNA supernatants can be used as a surrogate for thyroid molecular testing to improve diagnostic accuracy in indeterminate nodules, provide prognostic/predictive information, and improve overall patient management.
分子检测被推荐作为一种辅助手段，以提高细针穿刺（FNA）甲状腺结节的术前诊断。最近，FNA 样本的离心上清液作为一种新的液体活检方法用于分子检测。本研究评估了使用甲状腺 FNA 上清液检测临床相关突变的情况。
评估了 156 例甲状腺 FNA 样本的上清液。使用了 50 基因下一代测序（NGS）检测，对部分样本的突变分析结果与配对的 FNA 涂片和/或细胞块进行了进一步比较。
所有 156 例样本均获得了足够的 DNA（中位数为 135ng；范围为 11-3180ng），其中 129 例（83%）成功通过 NGS 测序。最常检测到的体细胞突变包括 BRAF 和 RAS 突变，其次是 RET、TP53、PTEN、CDKN2A 和 PIK3CA 突变。31 例不确定细胞学诊断和 12 例可疑恶性病例中有 11 例和 9 例分别检测到体细胞突变，包括高度明确的甲状腺乳头状癌（PTC）的 BRAF V600E 突变。9 例有 BRAF V600E 突变的不确定和可疑病例中有 7 例进行了手术随访，均被证实为 PTC。在一个小样本病例（n=8）中，对来自上清液的突变谱与配对的涂片和/或细胞块进行了比较，结果显示 100%一致。
本研究提供了证据表明，FNA 上清液可作为甲状腺分子检测的替代物，以提高不确定结节的诊断准确性，提供预后/预测信息，并改善整体患者管理。
