Gustavo C Penna1,2, Ana Pestana3,4, José Manuel Cameselle4,5, Denise Momesso1,6, Fernanda Accioly de Andrade1,6, Ana Paula Aguiar Vidal1, Mario Lucio Araujo Junior6, Miguel Melo3,4,7,8, Priscila Valverde Fernandes6, Rossana Corbo6, Mario Vaisman1, Manuel Sobrinho-Simões3,4,9,10, Paula Soares3,4,9, Fernanda Vaisman11,12. 1. Programa de Pós Graduação em Endocrinologia da Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 2. Clínica Endocrinológica do Hospital Mater Dei, Belo Horizonte, Brazil. 3. Instituto de Investigação e Inovação em Saúde (I3S), Porto, Portugal. 4. Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal. 5. Department of Pathology, Clinical University Hospital, SERGAS, Medical Faculty, University of Santiago de Compostela, Santiago de Compostela, Spain. 6. Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. 7. Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. 8. Unit of Endocrinology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 9. Department of Pathology, Medical Faculty, University of Porto, Porto, Portugal. 10. Department of Pathology, Hospital de S. João, Al. Prof. Hernâni Monteiro, Porto, Portugal. 11. Programa de Pós Graduação em Endocrinologia da Faculdade de Medicina da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. fevaisman@globo.com. 12. Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. fevaisman@globo.com.
Abstract
PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.
PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS:TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.
Entities:
Keywords:
Aggressive variants; Genetics; Persistent; Progression; TERT; Thyroid cancer
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