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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.
- Source :
-
Endocrine [Endocrine] 2018 Sep; Vol. 61 (3), pp. 489-498. Date of Electronic Publication: 2018 Jun 15. - Publication Year :
- 2018
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adenocarcinoma, Follicular mortality
Adenocarcinoma, Follicular pathology
Adolescent
Adult
Aged
Aged, 80 and over
Disease Progression
Female
Humans
Male
Middle Aged
Prognosis
Progression-Free Survival
Promoter Regions, Genetic
Thyroid Neoplasms mortality
Thyroid Neoplasms pathology
Time Factors
Young Adult
Adenocarcinoma, Follicular genetics
Mutation
Telomerase genetics
Thyroid Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0100
- Volume :
- 61
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Endocrine
- Publication Type :
- Academic Journal
- Accession number :
- 29948935
- Full Text :
- https://doi.org/10.1007/s12020-018-1642-0