The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.
本研究旨在分析联合评估结节超声风险类别（采用EU-TIRADS系统评估）、BRAF V600E突变状态及特定微小RNA（miR-146b、miR-221和miR-222）表达对Bethesda III类甲状腺结节的诊断价值，并分别针对具有核非典型性（AUS-核型）与其他类型非典型性（AUS-其他型）的病例进行探讨。我们共评估了161个术后已知组织病理学结果的结节（66个AUS-核型，95个AUS-其他型）。AUS-核型组的癌症检出率及癌症中乳头状甲状腺癌（PTC）的比例均约为AUS-其他型组的三倍。对于AUS-核型结节，最有效的诊断组合包括重复细针穿刺活检、BRAF V600E突变检测以及miR-146b和miR-222表达评估（敏感性：93.5%，特异性：80.0%）。对于AUS-其他型结节，最有效的诊断策略为两步法：第一阶段对重复细针穿刺结果为良性的患者暂缓手术治疗；第二阶段联合评估miR-222表达与EU-TIRADS分类（敏感性：92.3%，特异性：76.8%）。在III类甲状腺结节的诊断中，分子检测方法的最优应用需针对核非典型性结节与其他类型非典型性结节采取差异化策略。
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