Yoon Jung Hyun, Kwon Hyeong Ju, Lee Hye Sun, Kim Eun-Kyung, Moon Hee Jung, Kwak Jin Young
Department of Radiology, Severance Hospital, Research Institute of Radiological Science (JHY, E-KK, HJM, JYK); Department of Pathology, Yonsei University, College of Medicine (HJK); Department of Pathology, Yonsei University, Wonju College of Medicine (HJK); and Biostastistics Collaboration Unit, Medical Research Center, Yonsei University, College of Medicine (HSL), Seoul, South Korea.
Medicine (Baltimore). 2015 Jul;94(27):e1084. doi: 10.1097/MD.0000000000001084.
The object of this study is to evaluate the additional role of RAS mutation in detecting thyroid malignancy among BRAF mutation-negative nodules diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) on cytology.From December 2009 to December 2011, 202 BRAF mutation-negative thyroid nodules diagnosed as AUS/FLUS cytology in 201 patients were included in this study. RAS mutation analysis was performed using residual material from ultrasonography-guided fine needle aspiration (US-FNA) cytology testing for K-RAS, N-RAS, and H-RAS codons 12/13 and 61 point mutations. The authors evaluated the association between RAS mutation status and cytopathologic characteristics.Of the 202 BRAF mutation-negative thyroid nodules with AUS/FLUS cytology, 4 were considered insufficient for mutation analysis. Of the 198 thyroid nodules, 148 (74.7%) were confirmed as benign and 50 (25.3%) as malignant. Thirty-one (15.7%) of the 198 thyroid nodules were positive for any RAS mutation, 4 positive for K-RAS 12/13, 26 for N-RAS 61, and 1 positive for H-RAS 61. Seven (22.6%) of the RAS mutation positive nodules were malignant, 1 with K-RAS 12/13, 6 with N-RAS 61. Twenty-four (77.4%) of the 31 nodules positive for K-RAS 12/13 (N = 3), N-RAS 61 (N = 20), or H-RAS 61 (N = 1) mutations were proven benign. None of the 198 thyroid nodules were positive for K-RAS 61, N-RAS 12/13, or H-RAS 12/13 mutations.N-RAS 61 mutation is the most common mutation detected among BRAF mutation-negative nodules with AUS/FLUS cytology. RAS mutation has limited value in predicting malignancy among BRAF mutation-negative thyroid nodules with AUS/FLUS cytology and further, investigation is anticipated to evaluate the true role of RAS mutation in thyroid malignancy.
本研究的目的是评估RAS突变在检测经细胞学诊断为意义不明确的非典型性/意义不明确的滤泡性病变（AUS/FLUS）的BRAF突变阴性结节中的附加作用。2009年12月至2011年12月，本研究纳入了201例经细胞学诊断为AUS/FLUS的BRAF突变阴性甲状腺结节。使用超声引导下细针穿刺（US-FNA）细胞学检测的剩余材料对K-RAS、N-RAS和H-RAS密码子12/13及61位点突变进行RAS突变分析。作者评估了RAS突变状态与细胞病理学特征之间的关联。在202例经细胞学诊断为AUS/FLUS的BRAF突变阴性甲状腺结节中，4例被认为不足以进行突变分析。在198个甲状腺结节中，148个（74.7%）被确认为良性，50个（25.3%）为恶性。198个甲状腺结节中有31个（15.7%）存在任何RAS突变阳性，4个K-RAS 12/13阳性，26个N-RAS 61阳性，1个H-RAS 61阳性。RAS突变阳性结节中有7个（22.6%）为恶性，1个K-RAS 12/13阳性，6个N-RAS 61阳性。在31个K-RAS 12/13（N = 3）、N-RAS 61（N = 20）或H-RAS 61（N = 1）突变阳性的结节中，24个（77.4%）被证实为良性。198个甲状腺结节中无K-RAS 61、N-RAS 12/13或H-RAS 12/13突变阳性。N-RAS 61突变是在经细胞学诊断为AUS/FLUS的BRAF突变阴性结节中检测到的最常见突变。RAS突变在预测经细胞学诊断为AUS/FLUS的BRAF突变阴性甲状腺结节的恶性方面价值有限，因此需要进一步研究以评估RAS突变在甲状腺恶性肿瘤中的真正作用。
