title: RAS Mutations in AUS/FLUS Cytology: Does it Have an Additional Role in BRAFV600E Mutation-Negative Nodules?
abstract: 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.
authors.affiliation: 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.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hyeong Ju
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Moon
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kwak
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology*