Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules

Context: Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diag-nosis in thyroid nodules. However, 10–40 % of nodules are diagnosed as indeterminate by cytol-ogy, making it difficult to optimally manage these patients. Objective:Theaimof this studywas toestablish the feasibility and roleof testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules. Design: The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPAR mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months). Results:Asufficient amountofnucleic acidswere isolated in 98%of samples. Thirty-twomutations were found, including 18BRAF, eightRAS, fiveRET/PTC, andone PAX8/PPAR. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed sig-nificant improvement in the diagnostic accuracy and allowed better prediction of malignancy i