BRAFV600E Mutation Analysis in Fine-Needle Aspiration Cytology Specimens for Evaluation of Thyroid Nodule: A Large Series in aBRAFV600E-Prevalent Population

BACKGROUND: The BRAFV600E mutation is highly specific to papillary thyroid carcinoma. A test for this mutation may increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), especially in a BRAFV600E mutation-prevalent population. METHODS: This prospective study enrolled 1074 patients with thyroid nodules who underwent both FNAC and BRAFV600E mutation analysis by dual-priming oligonucleotide (DPO)-based multiplex PCR in FNA specimens. RESULTS: The ancillary test for BRAFV600E significantly improved the sensitivity of FNA procedure, from 67.5% with FNAC alone to 89.6% with FNAC and the DPO-based multiplex PCR analysis combined. Diagnostic accuracy increased from 90.9 to 96.6%. Nine cases of papillary thyroid carcinoma were detected only by BRAFV600E mutation analysis. Unexpectedly, the preoperative DPO-based multiplex PCR produced five false-positive results, which surgery showed to represent benign nodules. CONCLUSIONS: Molecular testing for the BRAFV600E mutation in FNA thyroid nodule specimens increases diagnostic value when applied in a BRAFV600E mutation-prevalent population. However, when using this potentially powerful technique, we must consider both its strengths and its weaknesses.