Division of Anatomic Pathology and Histology, "Agostino Gemelli" School of Medicine, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy.
Endocrine. 2016 Dec;54(3):723-732. doi: 10.1007/s12020-016-0866-0. Epub 2016 Jan 27.
Fine needle aspiration cytology (FNAC) plays an essential role in the evaluation of thyroid nodules especially for the category of follicular neoplasms (FN) representing 25 % of all thyroid cases including different neoplastic entities. Hence, one of the most promising areas is the application of molecular tests to FNAC. Among them, microRNAs (miRNA),identified as negative (post-transcriptional) gene expression regulators involved in tumor development, are likely to discriminate among FNs. Limited data explored the use of miRNAs on FNAC as well as their role in the malignant risk stratification. We aimed to define whether liquid-based cytology (LBC) is a valid method for miRNA evaluation. From June 2014 to March 2015, we enrolled 27FNs with histological follow-up. In the same reference period, 13 benign nodules (BN) and 20 positive for malignancy (PM) were selected as controls. Histologically, FNs resulted in 14 malignancies (3 papillary thyroid carcinoma-PTC and 11 follicular variant of PTC-FVPC) and 13 follicular adenomas (FA). The 20 PMs included two FVPC, 16 PTC and two medullary thyroid carcinoma (MTC). Five miRNAs (10b, 92a, 221/222 cluster, and 375) were studied on LBC and quantified by real-time PCR. Only miR-375 was over-expressed in the FNs diagnosed as carcinomas and in the PMs. A cut-off of 12 miR-375/U6 relative ratio recognized all BNs and 95 % PMs. Specifically, in each category, FVPCs and PTCs did not show any difference while MTCs had the highest value. miR-375 shows 97.1 % sensitivity, 100 % specificity, 96.3 % negative predictive value (NPV), 100 % positive predictive value (PPV), and 98.3 % diagnostic accuracy. LBC is suitable for miRNAs evaluation. miR-375 resulted over-expressed in all malignant FNs and 95 % PMs. It may represent a valid aid in ruling out BNs and supporting PTCs and/or FVPCs.
细针抽吸细胞学（FNAC）在评估甲状腺结节，特别是滤泡性肿瘤（FN）类别中起着至关重要的作用，FN 占所有甲状腺病例的 25％，包括不同的肿瘤实体。因此，最有前途的领域之一是将分子检测应用于 FNAC。其中，microRNAs（miRNA）被鉴定为参与肿瘤发展的负（转录后）基因表达调节剂，可能有助于区分 FN。有限的数据探讨了在 FNAC 中使用 miRNA 及其在恶性风险分层中的作用。我们旨在确定液基细胞学（LBC）是否是 miRNA 评估的有效方法。从 2014 年 6 月至 2015 年 3 月，我们纳入了 27 例具有组织学随访的 FN。在同一参考期间，选择 13 例良性结节（BN）和 20 例恶性结节（PM）作为对照。组织学上，FN 结果为 14 例恶性肿瘤（3 例甲状腺乳头状癌-PTC 和 11 例滤泡变体 PTC-FVPC）和 13 例滤泡性腺瘤（FA）。20 例 PM 包括 2 例 FVPC、16 例 PTC 和 2 例甲状腺髓样癌（MTC）。在 LBC 上研究了 5 种 miRNA（10b、92a、221/222 簇和 375），并通过实时 PCR 进行定量。仅在诊断为癌的 FN 和 PM 中发现 miR-375 过度表达。miR-375/U6 相对比值的截断值可识别所有 BN 和 95％的 PM。具体而言，在每个类别中，FVPC 和 PTC 之间没有差异，而 MTC 的值最高。miR-375 的灵敏度为 97.1％，特异性为 100％，阴性预测值（NPV）为 96.3％，阳性预测值（PPV）为 100％，诊断准确率为 98.3％。LBC 适用于 miRNA 评估。miR-375 在所有恶性 FN 和 95％的 PM 中过度表达。它可能是排除 BN 并支持 PTC 和/或 FVPC 的有效辅助手段。
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