Relevance of BRAF and NRAS mutations in the primary tumor and metastases of papillary thyroid carcinomas

Background. Multifocality of papillary thyroid carcinoma (PTC) is common. BRAF and NRAS mutations are the most frequent genetic alterations in PTC. The purpose of this study was to determine the distribution and relevance of BRAFT1799A and NRAS mutations in PTC. Methods. BRAFT1799A and NRAS mutations were evaluated in 195 intrathyroid or metastatic foci from 29 patients with multifocal PTC. Results. BRAFT1799A mutation was positive in 46.7% of the 59 intrathyroid and 136 metastatic foci (91/195 foci). Heterogeneous BRAF pattern was observed in 51.7% patients (15/29 patients). Irrespective of BRAF status at diagnosis (thyroid or nodes), all patients with recurrent PTC presented BRAF-mutated metastases during follow-up. All foci were negative for NRAS mutations. Conclusion. BRAF but not NRAS mutations were heterogeneously distributed among primary tumor, nodal sites, and recurrent disease. The BRAF status of metastases generated during the follow-up can differ from the status of foci at diagnosis. (C) 2016 Wiley Periodicals, Inc.