Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype.
Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNM) and distant metastases.
Material and Methods: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTC) (n=180), including 196 LNM and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue.
Results: We found the following mutation frequency in primary thyroid tumors, LNM and distant metastases, respectively: TERTp- 15.9, 10.8, and 52.4%; BRAF (PTC-only)- 44.6, 41.7, and 23.8%; NRAS- 1.7, 1.3, and 11.9%. In the subgroup of patients with PTC, the TERTp mutation frequency in primary tumors, LNM and distant metastases was 12.9, 10.5, and 52.4%, respectively. There was a significant concordance between the primary tumor genotype and the corresponding LNM, in particular for BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTC, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison to the paired primary tumors.
Conclusions: The frequency of BRAF, NRAS and TERTp mutations is similar in primary tumors and matched LNM, whereas distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations seem to play an important role in distant metastases.
20 - 23 May 2017
European Society of Endocrinology