Fine Needle Aspiration Analysis of B-RAF in Thyroid Nodules

Abstract

Objective Fine needle aspiration (FNA) represents the most useful initial diagnostic tool with which to analyze thyroid nodules for carcinoma. A mutation of the B-type RAF kinase (BRAF) represents the most common genetic alteration in sporadic papillary thyroid cancer (PTC), and may signify a more aggressive biological behavior within PTCs. Our objective was to determine if BRAF analysis of FNA cytology may provide clinically useful information in the analysis of thyroid nodules. Methods An IRB-approved retrospective chart review of clinically relevant data for classic PTCs (CPTC), follicular-variant of PTC (FV-PTC), or non-malignant goiter was performed following a blinded pathologic re-review. Both pathologic and cytology samples were analyzed by fluorescent melting curve analysis (FMCA) for the V600E mutation of BRAF, and mutational status was compared with clinical information. Results A 100% concordance was found for BRAF mutation determination between the cytologic and final pathologic malignant and benign tissue samples studied. BRAF mutation was found to be significantly higher in papillary carcinomas when compared to follicular-variant of papillary thyroid carcinomas (55.6% vs. 14.3%, p=0.05), and correlated with cytologic interpretation (p=0.025) and histologic diagnosis (p=0.03). Conclusions FMCA of thyroid nodule FNAs can accurately determine the mutational status of the BRAF gene. Since the presence of BRAF mutation can predict a more aggressive biological behavior, an analysis of BRAF mutational status of initial FNAs may add useful information to the list of risk stratification criteria for PTCs.