<i>RAS</i> Mutations in AUS/FLUS Cytology: Does it Have an Additional Role in BRAF ^V600E Mutation-Negative Nodules?

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P><P>The object of this study is to evaluate the additional role of <I>RAS</I> mutation in detecting thyroid malignancy among BRAF<SUP>V600E</SUP> mutation-negative nodules diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) on cytology.</P><P>From December 2009 to December 2011, 202 BRAF<SUP>V600E</SUP> mutation-negative thyroid nodules diagnosed as AUS/FLUS cytology in 201 patients were included in this study. <I>RAS</I> mutation analysis was performed using residual material from ultrasonography-guided fine needle aspiration (US-FNA) cytology testing for <I>K-RAS</I>, <I>N-RAS</I>, and <I>H-RAS</I> codons 12/13 and 61 point mutations. The authors evaluated the association between <I>RAS</I> mutation status and cytopathologic characteristics.</P><P>Of the 202 BRAF<SUP>V600E</SUP> 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 <I>RAS</I> mutation, 4 positive for <I>K-RAS</I> 12/13, 26 for <I>N-RAS</I> 61, and 1 positive for <I>H-RAS</I> 61. Seven (22.6%) of the <I>RAS</I> mutation positive nodules were malignant, 1 with <I>K-RAS</I> 12/13, 6 with <I>N-RAS</I> 61. Twenty-four (77.4%) of the 31 nodules positive for <I>K-RAS</I> 12/13 (N = 3), <I>N-RAS</I> 61 (N = 20), or <I>H-RAS</I> 61 (N = 1) mutations were proven benign. None of the 198 thyroid nodules were positive for <I>K-RAS</I> 61, <I>N-RAS</I> 12/13, or <I>H-RAS</I> 12/13 mutations.</P><P><I>N-RAS</I> 61 mutation is the most common mutation detected among BRAF<SUP>V600E</SUP> mutation-negative nodules with AUS/FLUS cytology. <I>RAS</I> mutation has limited value in predicting malignancy among BRAF<SUP>V600E</SUP> mutation-negative thyroid nodules with AUS/FLUS cytology and further, investigation is anticipated to evaluate the true role of <I>RAS</I> mutation in thyroid malignancy.</P>