Dataset Information

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

ABSTRACT:

Background

A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial.

Objective

The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation.

Methods

A total of 87 FTC patients who had information about TERT promoter mutation from August 1995 to November 2020 were investigated. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each of the World Health Organization (WHO) 2017 classifications were calculated.

Results

Of the 87 patients, 8 (9.2%) had initial distant metastasis and 15 (17.2%) had persistent disease or developed structural recurrence. The threshold diameter for initial distant metastasis, disease recurrence, and cancer-specific death was 2 cm in minimally invasive FTC (MI-FTC) with mutant TERT (M-TERT) and in encapsulated angioinvasive FTC (EA-FTC) with M-TERT, while that in MI-FTC with wild-type TERT (WT-TERT) and EA-FTC with WT-TERT was 4 cm. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each WHO 2017 classification was significantly different only in patients with WT-TERT (p = 0.001, p = 0.019, and p = 0.005, respectively).

Conclusions

The data suggest 2 cm as a critical threshold diameter for performance of completion thyroidectomy in MI-FTC with M-TERT and EA-FTC with M-TERT. TERT promoter mutational status can help select candidates for completion thyroidectomy.

SUBMITTER: Park H

PROVIDER: S-EPMC9838536 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

Park Hyunju H Heo Jung J Ki Chang-Seok CS Shin Jung Hee JH Oh Young Lyun YL Son Young Ik YI Kim Jee Soo JS Kim Sun Wook SW Chung Jae Hoon JH Kim Tae Yong TY Kim Tae Hyuk TH Kim Jung-Han JH

Annals of surgical oncology 20230113 5

<h4>Background</h4>A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial.<h4>Objective</h4>The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation.<h4>Methods</h4>A total of 87 FTC patients who had informati ...[more]

PMID: 36637642

Similar Datasets

Project description:BackgroundDNA hypermethylation and hotspot mutations were frequently observed in the upstream and core promoter of telomerase reverse transcriptase (TERT), respectively, and they were associated with increased TERT expression and adverse clinical outcomes in thyroid cancer. In TERT promoter mutant cancer cells, the hypomethylated TERT mutant allele was active and the hypermethylated TERT wild-type allele was silenced. However, whether and how the upstream promoter methylation regulates TERT expression in TERT mutation-negative cells were largely unknown.MethodsDNA demethylating agents 5-azacytidine and decitabine and a genomic locus-specific demethylation system based on dCas9-TET1 were used to assess the effects of TERT upstream promoter methylation on TERT expression, cell growth and apoptosis of thyroid cancer cells. Regulatory proteins binding to TERT promoter were identified by CRISPR affinity purification in situ of regulatory elements (CAPTURE) combined with mass spectrometry. The enrichments of selected regulatory proteins and histone modifications were evaluated by chromatin immunoprecipitation.ResultsThe level of DNA methylation at TERT upstream promoter and expression of TERT were significantly decreased after treatment with 5-azacytidine or decitabine in TERT promoter wild-type thyroid cancer cells. Genomic locus-specific demethylation of TERT upstream promoter induced TERT downregulation, along with cell apoptosis and growth inhibition. Consistently, demethylating agents sharply inhibited the growth of thyroid cancer cells harboring hypermethylated TERT but had little effect on cells with TERT hypomethylation. Moreover, we identified that the chromatin remodeling protein CHD4 binds to methylated TERT upstream promoter and promotes its transcription by suppressing the enrichment of H3K9me3 and H3K27me3 at TERT promoter.ConclusionsThis study uncovered the mechanism of promoter methylation mediated TERT activation in TERT promoter mutation-negative thyroid cancer cells and indicated TERT upstream promoter methylation as a therapeutic target for thyroid cancer.

Dataset Information

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

Background

Objective

Methods

Results

Conclusions

Publications

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

Similar Datasets

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