Nikiforov Yuri E, Steward David L, Robinson-Smith Toni M, Haugen Bryan R, Klopper Joshua P, Zhu Zhaowen, Fagin James A, Falciglia Mercedes, Weber Katherine, Nikiforova Marina N
Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
J Clin Endocrinol Metab. 2009 Jun;94(6):2092-8. doi: 10.1210/jc.2009-0247. Epub 2009 Mar 24.
Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diagnosis in thyroid nodules. However, 10-40% of nodules are diagnosed as indeterminate by cytology, making it difficult to optimally manage these patients.
The aim of this study was to establish the feasibility and role of testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules.
The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPARgamma mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months).
A sufficient amount of nucleic acids were isolated in 98% of samples. Thirty-two mutations were found, including 18 BRAF, eight RAS, five RET/PTC, and one PAX8/PPARgamma. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed significant improvement in the diagnostic accuracy and allowed better prediction of malignancy in the nodules with indeterminate cytology.
These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology.
甲状腺结节在成年人中很常见，但其中只有一小部分是恶性的。细针穿刺活检（FNA）及细胞学评估是甲状腺结节癌症诊断最可靠的工具。然而，10%至40%的结节通过细胞学检查被诊断为意义不明确，这使得对这些患者进行最佳管理变得困难。
本研究的目的是确定检测肿瘤特异性突变在改善甲状腺结节FNA诊断中的可行性和作用。
这项前瞻性研究纳入了328例患者的470份甲状腺结节FNA样本。穿刺时，收集一小部分样本材料，检测BRAF、RAS、RET/PTC和PAX8/PPARγ突变。将突变状态与细胞学检查结果以及手术病理诊断或随访结果（平均34个月）进行关联分析。
98%的样本中分离出了足够量的核酸。共发现32个突变，包括18个BRAF突变、8个RAS突变、5个RET/PTC突变和1个PAX8/PPARγ突变。任何突变的存在都是癌症的有力指标，因为31个（97%）突变阳性结节术后被诊断为恶性。细胞学检查与分子检测相结合显著提高了诊断准确性，并能更好地预测细胞学检查结果意义不明确的结节的恶性程度。
这些结果表明，在临床环境中可以有效地对甲状腺结节进行一组突变的分子检测。它提高了FNA细胞学检查的准确性，对于细胞学检查结果意义不明确的甲状腺结节具有特别的价值。
