BRAF(V600E) mutation analysis in fine‐needle aspiration cytology specimens for diagnosis of thyroid nodules: The influence of false‐positive and false‐negative results

BACKGROUND: The accurate evaluation of BRAF(V600E) mutation in preoperative fine‐needle aspiration cytology (FNAC) specimens is important for making management decisions in thyroid nodules (TNs). The aim of this study was to assess the false‐positive and false‐negative BRAF(V600E) mutations in thyroid FNAC specimens and their influence on diagnosis of TN. METHODS: This prospective study enrolled 292 nodules in 269 patients who underwent BRAF(V600E) mutation analysis using amplification refractory mutation system‐quantitative real‐time polymerase chain reaction (ARMS‐qPCR) both in FNAC specimens and formalin‐fixed, paraffin‐embedded (FFPE) tissue samples after surgery. The false‐positive and false‐negative mutations for BRAF(V600E) analysis using ARMS‐qPCR in FNAC specimens were recorded, with reference to the results of BRAF(V600E) mutation analysis using ARMS‐qPCR in FFPE tissue sample. Diagnostic performances of FNAC, BRAF(V600E) mutation analysis in FNAC specimens, BRAF(V600E) mutation analysis in FFPE tissue sample, and the combination of FNAC and BRAF(V600E) mutation analysis for predicting thyroid malignancy were assessed. RESULTS: The false‐positive and false‐negative mutations for BRAF(V600E) analysis using ARMS‐qPCR in FNAC specimens were 10.1% (19/189) and 7.1% (7/98), respectively. FNAC combined with preoperative BRAF(V600E) mutation analysis significantly increased the diagnostic sensitivity from 75.7% to 92.3%, and accuracy from 78.7% to 90.6% in comparison with FNAC alone (both P < .001). No significant differences were found between the combination of FNAC and BRAF(V600E) mutation analysis in FNAC specimens and the combination of FNAC and BRAF(V600E) mutation analysis in FFPE tissue sample (sensitivity: 92.3% vs 91.9%; accuracy: 90.6% vs 91.3%; both P > .05). CONCLUSIONS: FNAC combined with preoperative BRAF(V600E) mutation analysis can significantly increase the diagnostic performance in comparison with FNAC alone. False‐positive and false‐negative BRAF(V600E) mutation results are found in preoperative FNAC specimens, whereas it does not affect the overall auxiliary diagnosis of TNs.