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TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma

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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.

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Acknowledgements

This study was supported by a CNPq PhD Scholarship (“National Counsel of of Technological and Scientific Development”, Brazil), Science Without Borders, and CAPES Foundation Ministry of Education of Brazil, Brasilia—DF 70.040-020, Brazil, Process No. BEX6726/15-1 to G.P. This work was financed by FEDER, Fundo Europeu de Desenvolvimento Regional, funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Further funding from the project “Advancing cancer research: from basic Knowledgement to application”; NORTE-01-0145-FEDER-000029; “Projetos Estruturados de I&D&I”, funded by Norte 2020 – Programa Operacional Regional do Norte.

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Correspondence to Fernanda Vaisman.

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These authors contributed equally: Gustavo C. Penna, Ana Pestana.

These authors jointly supervised this work: Paula Soares and Fernanda Vaisman.

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Penna, G.C., Pestana, A., Cameselle, J.M. et al. TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma. Endocrine 61, 489–498 (2018). https://doi.org/10.1007/s12020-018-1642-0

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