BRAFV600E analysis on fine needle aspiration biopsy increases diagnostic accuracy for papillary thyroid cancer in clinically unsuspected nodules
Martina Rossi1, Giorgio Trasforini1, Stefania Leoni1, Federico Tagliati1, Roberta Rossi1, Elio Roti2, Ettore C degli Uberti1 & Maria Chiara Zatelli1
Papillary thyroid cancer (PTC) represents the majority of differentiated thyroid cancers, presenting in 2983% of cases the activating BRAF V600E mutation. The aim of our study was to analyse the influence of BRAF V600E mutation analysis on diagnostic accuracy of fine needle aspiration biopsies (FNAB) in clinically unsuspected thyroid nodules. We therefore enrolled 496 patients (383 females, 113 males; mean age 52 years), for a total of 671 samples. FNAB were evaluated by the cytologist and the syringe wash out was employed for BRAF mutation analysis, performed after DNA isolation by direct sequencing and allelic discrimination. Among the 671 samples, BRAF V600E mutation was found 34, including 24 diagnosed as PTC also citology-wise (also confirmed by histology). Total thyroidectomy was also performed in 10 patients with BRAF V600E mutation but negative cytology, all confirmed as PTC at histology. Among the 637 samples with negative BRAF V600E mutation, 629 had benign citology, while 8 were consistent with PTC then confirmed by histology. Statistical analysis showed an incidence of 74% for the BRAF V600E mutation in PTC cases; sensitivity was 73.9% and specificity was 100%. Positive and negative predictive values were 100 and 98.1%, respectively. Diagnostic accuracy of cytology was 97.9%, and increate to 99.4% when combined with BRAF mutation analysis. These data indicate that BRAF V600E mutation analysis can significantly improve diagnostic accuracy in clinically unsuspected cases. On the other hand biomolecular analysis is complimentary to citology, since it is not sufficient to diagnose every malignant case.