Mutation profiling of thyroid liquid-based fine needle aspirations improves diagnostic accuracy

Abstract

Fine needle aspiration (FNA) is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. Recently use of molecular biomarkers was proposed to improve pathologic accuracy. We evaluated feasibility and performance of molecular analysis in liquid-based FNA (LB-FNA) with indeterminate cytology. Mutation profiling of NRAS, HRAS and BRAF was performed on residual material from LB-FNA of 215 cases including 83 atypia of undetermined significance (AUS), 72 follicular neoplasms (FN), 46 suspicious for malignancy (SM), and 14 malignant (M). Forty-eight (22%) cases were mutated. Twenty-four cases presented a RAS mutation (19 NRAS and 5 HRAS) (11 AUS, 6 FN, and 7 SM) and 24 were carrying a BRAF mutation (1FN, 11 SM, and 12M). Surgical samples were available for 38 cases: 3 AUS, 14 FN, 13 SM and 8M. In the AUS category, 1 was a papillary carcinoma (PC) with NRAS mutation and 2 were benign (1 with NRAS mutation). In the FN category, 3 were malignant (1 with BRAF and 1 with HRAS mutation) and 11 benign (1 with HRAS and 1 with NRAS mutation). In the SM group, 10 were PC (3 with NRAS mutation and 5 with BRAF mutation) and 3 benign (no mutation). In the M group, all were PC with BRAF mutation. In conclusion, mutation profiling of BRAF and RAS can be successfully performed on residual material of thyroid LB-FNA and could improve the diagnostic accuracy of FNA.