Department of Nuclear Medicine and Thyroid Unit, Centre François Baclesse, Caen, France.
Department of Molecular Biology, Centre François Baclesse, Caen, France.
Endocrine. 2021 Feb;71(2):407-417. doi: 10.1007/s12020-020-02411-4. Epub 2020 Jul 7.
The aim of this prospective study (ClinicalTrials.gov: NCT01880203) was to evaluate the diagnostic and prognostic value of a 7-panel mutation testing in the aspirates of thyroid nodules with indeterminate cytology (IC).
Eligible patients had a thyroid nodule ≥15 mm with IC (Bethesda III-V) for which surgery had been recommended. Detection of BRAF and RAS mutations was performed using pyrosequencing and RET/PTC and PAX8/PPARγ rearrangements using Real-Time quantitative reverse transcription-polymerase chain reaction (RT-PCR).
Among 131 nodules with IC, 21 (16%) were malignant including 20 differentiated cancers and one thyroid lymphoma. Molecular abnormalities were identified in 15 nodules with IC corresponding to 10 malignant and 5 benign tumours. BRAF mutation was detected in 4 nodules all corresponding to classic PTC, and PAX8/PPARγ rearrangement in 2 HCC. In contrast, RAS mutation was identified in eight nodules, of which four were malignant, and one RET/PTC3 rearrangement in a follicular adenoma. This data resulted in an accuracy of 88%, sensitivity of 48%, specificity of 95%, positive-predictive value of 67%, and negative-predictive value of 91%. After a 56 month's follow-up, the proportion of excellent response was similar in patients with molecular alterations (67%) and those without (60%).
By increasing the overall risk of cancer from 16 to 67% in mutated nodules and by diminishing it to 9% in wild-type, this study confirms the relevance of the 7-panel mutation testing in the diagnostic of nodules with IC. Genetic testing, however, did not predict outcome in the cancer patient subgroup.
本前瞻性研究（ClinicalTrials.gov：NCT01880203）旨在评估 7 -panel 突变检测在具有不确定细胞学（IC）的甲状腺结节抽吸物中的诊断和预后价值。
符合条件的患者有直径≥15mm 的甲状腺结节，伴有建议手术的 IC（Bethesda III-V）。使用焦磷酸测序检测 BRAF 和 RAS 突变，使用实时定量逆转录聚合酶链反应（RT-PCR）检测 RET/PTC 和 PAX8/PPARγ 重排。
在 131 个具有 IC 的结节中，有 21 个（16%）为恶性，包括 20 个分化癌和 1 个甲状腺淋巴瘤。在 15 个具有 IC 的结节中发现了分子异常，对应于 10 个恶性和 5 个良性肿瘤。在 4 个结节中均检测到 BRAF 突变，均对应于经典的 PTC，在 2 个 HCC 中检测到 PAX8/PPARγ 重排。相反，在 8 个结节中发现了 RAS 突变，其中 4 个为恶性，1 个滤泡性腺瘤中有 RET/PTC3 重排。这一数据导致准确率为 88%，灵敏度为 48%，特异性为 95%，阳性预测值为 67%，阴性预测值为 91%。经过 56 个月的随访，在有分子改变的患者（67%）和没有分子改变的患者（60%）中，优秀反应的比例相似。
通过将突变结节的总体癌症风险从 16%增加到 67%，并将野生型的风险降低到 9%，本研究证实了 7-panel 突变检测在诊断具有 IC 的结节中的相关性。然而，基因检测并没有预测癌症患者亚组的预后。
