Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic.
Department of Ear, Nose and Throat, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Thyroid. 2024 Oct;34(10):1225-1233. doi: 10.1089/thy.2024.0188. Epub 2024 Sep 27.
Recent studies have suggested that pathogenic variants of the gene could be a driver of alterations in some pediatric thyroid nodules, but data are still limited. The aim of this study was to detect variants in the gene in a large cohort of pediatric thyroid nodules and then correlate them with clinicopathological data, with a focus on the disease prognosis in patients with thyroid carcinoma. This retrospective cohort study consisted of 350 pediatric and young adult patients (aged 2-21 years) with thyroid nodules, from whom 275 fresh-frozen thyroid nodule samples and 92 fine-needle aspiration biopsy (FNAB) samples were collected. After an analysis of variants in major genetic alterations of thyroid tumors, variants in the gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with -positive tumors. The results of genetic analysis were then correlated with clinicopathological data. Variants in the gene were detected in a total of 24/350 (6.9%; 95%CI [4.4;10.0]) pediatric and young adult patients, respectively, in 10/119 (8.4%; [4.1;14.9]) patients with benign fresh-frozen tissue, in 8/141 (5.7%; [1.9;9.5]) with papillary thyroid carcinoma (PTC) and in 6/86 (7.0%; [4.1;14.6]) patients with FNAB. No other gene alteration was found in -positive samples. Germline variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the gene were found in 9/24 (37.5%; [18.8;59.4]) thyroid nodules. Somatic deletions of at least 3 Mbp long were revealed in 2/24 (8.3%; [1.0;27.0]) cases. -positive PTCs were significantly associated with the follicular subtype of PTC ( = 0.001), encapsulation ( = 0.006) and were larger in size ( = 0.035), but with no extrathyroidal extension ( = 0.039), and less frequent lymph node metastases ( = 0.003) compared with -negative PTCs. Patients with positive PTC had an excellent response to treatment in 75% of cases. Variants of the gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, -positive PTCs showed low invasiveness. Our findings support considering more conservative management for -positive low-risk PTCs.
最近的研究表明， 基因的致病变体可能是导致一些儿科甲状腺结节改变的驱动因素，但数据仍然有限。本研究的目的是在一个大的儿科甲状腺结节队列中检测 基因的变体，并将其与临床病理数据相关联，重点是甲状腺癌患者的疾病预后。这项回顾性队列研究纳入了 350 名儿科和年轻成年患者（年龄 2-21 岁）的甲状腺结节，其中 275 名患者采集了新鲜冷冻甲状腺结节样本，92 名患者采集了细针穿刺活检（FNAB）样本。在分析甲状腺肿瘤主要遗传改变中的变体后，使用下一代测序和多重连接依赖性探针扩增方法检测 基因中的变体。对 -阳性肿瘤患者进行外周血分析。然后将遗传分析结果与临床病理数据相关联。在总共 350 名儿科和年轻成年患者中，共检测到 24 名（6.9%；95%CI[4.4；10.0]）患者的 基因发生了变异，10 名（8.4%；[4.1；14.9]）良性新鲜冷冻组织患者，14 名（5.7%；[1.9；9.5]）甲状腺乳头状癌（PTC）患者和 86 名（7.0%；[4.1；14.6]）FNAB 患者中存在 基因的变异。在 -阳性样本中未发现其他基因突变。在 24 名患者中发现了 11 名（45.8%；[25.6；67.2%]）存在胚系 基因变异。在 24 名患者中发现了 2 名（37.5%；[18.8；59.4%]）甲状腺结节中存在体细胞（双等位基因）变异。在 2 名（8.3%；[1.0；27.0%]）患者中发现了至少 3 Mbp 长的体细胞缺失。-阳性 PTC 与 PTC 的滤泡亚型显著相关（ = 0.001），包膜（ = 0.006），并且更大（ = 0.035），但无甲状腺外延伸（ = 0.039），淋巴结转移（ = 0.003）较少。与 -阴性 PTC 相比，75%的阳性 PTC 患者对治疗有极好的反应。 在儿科和年轻成年患者的甲状腺结节中经常发现 基因的变异。在我们的患者中，-阳性 PTC 表现出低侵袭性。我们的研究结果支持对 -阳性低风险 PTC 进行更保守的管理。
