目的:不确定的甲状腺结节的处理仍然是一个正在进行辩论的话题,特别是关于恶性肿瘤的分化。体细胞突变分析提供了对肿瘤特征的重要见解。本研究旨在通过体细胞突变分析来辅助不确定结节的临床管理。
方法:本研究包括20个不确定的甲状腺结节的抽吸样本。包含67个基因的下一代测序小组用于分子谱分析。将结果与手术材料的病理数据进行比较,这被认为是黄金标准。灵敏度,特异性,阳性预测值(PPV),并计算阴性预测值(NPV)。
结果:六个基因的变异(NRAS,BRAF,TP53,TERT,PTEN,在20个样品中的10个中检测到PIK3CA)。我们在15个恶性结节中的10个(67%)中鉴定出9个一级或二级变异(NRAS,BRAF,TP53,TERT,PTEN,PIK3CA)和五个良性结节中的一个中的一个2级(PIK3CA)变体。研究表明,NPV为40%,90%的PPV,80%的特异性,灵敏度为60%。
结论:基于检测到的分子标记,至少9例患者(45%)可以在不需要重复FNAB尝试的情况下得到正确治疗.这项研究强调了分子测试在不确定细胞学检查中处理结节的临床实用性。此外,这项研究强调了在确定基于DNA或RNA的基因检测方法时考虑患者年龄的重要性.最后,我们讨论了体细胞突变谱的意义及其对当前病理分类的影响。
OBJECTIVE: The management of indeterminate thyroid nodules remains a topic of ongoing debate, particularly regarding the differentiation of malignancy. Somatic mutation analysis offers crucial insights into tumor characteristics. This study aimed to assist the clinical management of indeterminate nodules with somatic mutation analysis.
METHODS: Aspiration samples from 20 indeterminate thyroid nodules were included in the study. A next-generation sequencing panel containing 67 genes was used for molecular profiling. The results were compared with pathology data from surgical material, which is considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.
RESULTS: Variants in six genes (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) were detected in 10 out of 20 samples. We identified nine Tier 1 or 2 variants in 10 (67 %) out of 15 malignant nodules (NRAS, BRAF, TP53, TERT, PTEN, PIK3CA) and one Tier 2 (PIK3CA) variant in one out of five benign nodules. The study demonstrated an NPV of 40 %, a PPV of 90 %, a specificity of 80 %, and a sensitivity of 60 %.
CONCLUSIONS: Based on the detected molecular markers, at least nine patients (45 %) could be managed correctly without needing a repeat FNAB attempt. This study underscores the clinical practicality of molecular tests in managing nodules with indeterminate cytology. Additionally, this study emphasizes the importance of considering the patient\'s age when determining the DNA- or RNA-based genetic testing method. Finally, we discussed the significance of the somatic mutation profile and its impact on the current pathological classification.