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Co-existence of BRAFV600E and TERT promoter mutations in papillary thyroid carcinoma is associated with tumor aggressiveness, but not with lymph node metastasis

Authors Ren HY, Shen YF, Hu DX, He W, Zhou J, Cao YJ, Mao Y, Dou Y, Xiong W, Xiao Q, Zhang YH, Su XL

Received 12 December 2017

Accepted for publication 8 March 2018

Published 3 May 2018 Volume 2018:10 Pages 1005—1013

DOI https://doi.org/10.2147/CMAR.S159583

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Leylah Drusbosky


Haoyu Ren,1 Yifan Shen,2 Daixing Hu,1 Wei He,1 Jing Zhou,1 Yijia Cao,1 Yu Mao,1 Yi Dou,1 Wei Xiong,1 Qi Xiao,1 Yuhong Zhang,2 Xinliang Su1

1Department of Endocrine and Breast Surgery, 2The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Background: Mutations of BRAFV600E and TERT promoters are associated with thyroid cancer development. This study further investigated association of these mutations with clinicopathological characteristics from patients with papillary thyroid carcinoma (PTC).
Methods:
Tumor tissues from 342 PTC patients were obtained for DNA extraction and polymerase chain reaction amplification to detect the BRAFV600E mutation using amplification-refractory mutation system-polymerase chain reaction. TERT promoter mutations were assessed using Sanger DNA sequencing. The association of these gene mutations with clinicopathological characteristics was then statistically analyzed.
Results: Two hundred and seventy of 342 (78.9%) PTC patients harbored the BRAFV600E mutation, which was associated with older age male patients. Moreover, TERT promoter mutations occurred in 12 of 342 (3.5 %) PTC patients, all of whom also had the BRAF mutation. One hundred thirty-three patients with papillary thyroid microcarcinoma (PTMC) had no TERT mutations. Statistically, the coexistence of BRAF and TERT promoter mutations were significantly associated with older age, larger tumor size, extrathyroidal extension, and advanced tumor stage, but not with central lymph node metastasis, lateral lymph node metastasis, numbers of lymph node metastasis >5, and numbers of involved/harvested lymph nodes (No. of LNs involved or harvested). The multivariate analyses showed older age (odds ratio [OR], 2.194; 95% CI: 1.117–4.311; p=0.023), larger tumor size (OR, 4.100; 95% CI: 2.257–7.450; p<0.001), and multiplicity (OR, 2.240; 95% CI: 1.309–3.831; p=0.003) were all independent predictors for high prevalence of extrathyroidal extension. However, there was no statistical association with any clinicopathological characteristics except for Hashimoto thyroiditis in PTMC.
Conclusion: The current study demonstrated that the coexistence of BRAF and TERT promoter mutations were associated with the PTC aggressiveness, although these mutations were not associated with PTC lymph node metastasis or with PTMC.

Keywords: papillary thyroid carcinoma, TERT promoter mutation, BRAF mutation, clinicopathological features

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