Endocrine Abstracts (2017) 49 OC14.3 | DOI: 10.1530/endoabs.49.OC14.3

TERT, BRAF and NRAS in the molecular profile of metastatic thyroid cancer: differences between primary and distant disease

Miguel Melo1,2, Adriana Gaspar da Rocha1,3, Rui Batista1,4, Joao Vinagre1, Maria Joao Martins5, Gracinda Costa6, Cristina Ribeiro2, Francisco Carrilho2, Valeriano Leite7,8, Claudia Lobo9, Jose Manuel Cameselle-Teijeiro10, Manuel Sobrinho-Simoes1,11 & Paula Soares1,12

1Instituto de Investigação e Inovação em Saúde (I3S), Porto, Portugal; 2Department of Endocrinology – Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, 3Unidade de Saude Publica de Cantanhede, ACeS do Baixo Mondego, Cantanhede, Portugal; 4Medical Faculty, University of Porto, Porto, Portugal; 5Department of Pathology – Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 6Department of Nuclear Medicine – Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 7Unit for Investigation of Molecular Pathobiology, Portuguese Institute of Oncology – Lisbon Center, Lisboa, Portugal; 8Department of Endocrinology, Portuguese Institute of Oncology – Lisbon Center, Lisboa, Portugal; 9Department of Pathology, Portuguese Institute of Oncology – Porto Center, Porto, Portugal; 10Department of Pathology, Clinical University Hospital, SERGAS, Medical Faculty, University of Santiago de Compostela, Santiago de Compostela, Spain; 11Department of Pathology, Hospital S. João, Porto, Portugal; 12Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal.

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.