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Letter
Thyroid Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)
Sue Youn Kim1orcid, Chan Kwon Jung1,2orcid
Endocrinology and Metabolism 2022;37(6):947-948.
DOI: https://doi.org/10.3803/EnM.2022.1596
Published online: November 10, 2022

1Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea

2Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

Corresponding author: Chan Kwon Jung. Department of Hospital Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-1622, Fax: +82-2-2258-1627, E-mail: ckjung@catholic.ac.kr
• Received: September 28, 2022   • Accepted: October 4, 2022

Copyright © 2022 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See the letter-reply "Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients (Endocrinol Metab 2022;37:652-63, Heera Yang et al.)" in Volume 37 on page 949.
See the letter "Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients" on page 652.
We have read the article by Yang et al. [1] with great interest. They investigated real-world frequencies of telomerase reverse transcriptase (TERT) promoter mutations (C228T [chr5: 1,295,228C>T] and C250T [chr5: 1,295,250C>T]) in patients with thyroid carcinoma. We congratulate the authors on their work for prospectively collecting data for the largest cohort of patients with thyroid cancers ever reported. The frequency of TERT promoter mutations in the real-world was lower than that of previous studies performed retrospectively. After we first reported the low-frequency of TERT promoter mutations in prospectively enrolled patients with papillary thyroid carcinoma (PTC) in 2020 [2], several institutions have reported their data on TERT promoter mutation frequency in real-world analysis [1,3,4]. Therefore, we aimed to summarize real-world data on TERT promoter mutations in thyroid cancers.
Data of TERT promoter mutations prospectively collected from consecutive patients with thyroid cancers were available in four studies (Table 1). As molecular diagnostic test of TERT promoter mutation became available for patients with thyroid cancer in Korea in late 2018, all studies conducted in Korea included patients who had undergone the molecular test after 2018. Meta-analysis showed that pooled proportion of TERT promoter mutations was 2.6% (95% confidence interval [CI], 2.1 to 3.2) in all PTCs, 1.3% (95% CI, 0.5 to 2.6) in PTCs ≤1.0 cm, and 5.6% (95% CI , 4.4 to 7.0) in PTCs >1.0 cm (Table 1). There was no significant heterogeneity between studies (I2=0.0%) in the subgroup of PTCs >1.0 cm. Consistently low prevalence in the prospective cohorts of PTC patients contradicts pooled proportion of 11.3% (95% CI, 9.3 to 13.5) from 13 studies included in a previous meta-analysis [5].
In PTCs >1.0 cm, TERT promoter mutated cases were consistently associated with older age, larger size, lateral lymph node metastasis, and aggressive histologic features [1-3], in line with results from previous retrospective studies. On the other hand, there have been limited data on its prognostication role in PTCs ≤1.0 cm. Some studies have reported that status of TERT promoter mutation shows no association with aggressive clinicopathologic features in PTCs ≤1.0 cm, even in cases with coexisting BRAFV600E mutations [2,4]. However, only short-term follow-up has been done so far. A longer interval of surveillance for recurrence is required.
In conclusion, PTCs highly prevalent in Korea have a lower frequency of TERT promoter mutations than previously reported. The clinical utility of TERT promoter mutations as a prognostic marker has been validated in PTCs larger than 1.0 cm, but not in PTC ≤1.0 cm. We are grateful for the opportunity to review real-world data on frequency of TERT promoter mutations in patients with PTC.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Acknowledgements
This research was supported by a grant (NRF-2020R1F1A1070028) from the Basic Science Research Program through the National Research Foundation funded by the Ministry of Science and ICT, Republic of Korea.
Table 1.
Meta-Analysis of TERT Promoter Mutation Frequency in Prospectively Collected Patients with PTC
Study Data collection period PTC, all PTC ≤1.0 cm PTC >1.0 cm
Kim et al. (2020) [2] December 2018–December 2019 16/724 (2.2%) 5/518 (1.0%) 11/206 (5.3%)
Choi et al. (2021) [3] February 2019–December 2020 13/622 (2.1%) 4/415 (1.0%) 9/207 (4.3%)
Lee et al. (2021) [4] June 2019–October 2020 NA 16/504 (3.2%) NA
Yang et al. (2022) [1] January 2019–December 2020 57/2,020 (2.8%) 6/1,143 (0.5%) 51/877 (5.8%)
Total sample size 3,366 2,580 1,290
Pooled proportion (95% CI) 2.6% (2.1–3.2)a 1.3% (0.5–2.6)b 5.6% (4.4–7.0)a
Heterogeneity P=0.526, I2 =0.0% P=0.001, I2 =81.1% P=0.748, I2 =0.0%

TERT, telomerase reverse transcriptase; PTC, papillary thyroid carcinoma; NA, not available; CI, confidence interval; I, inconsistency.

a A fixed effect model was used for meta-analysis;

b A random effect model was used for meta-analysis.

  • 1. Yang H, Park H, Ryu HJ, Heo J, Kim JS, Oh YL, et al. Frequency of TERT promoter mutations in real-world analysis of 2,092 thyroid carcinoma patients. Endocrinol Metab (Seoul) 2022;37:652–63.ArticlePubMedPMCPDF
  • 2. Kim SY, Kim T, Kim K, Bae JS, Kim JS, Jung CK. Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans. J Pathol Transl Med 2020;54:310–7.ArticlePubMedPMCPDF
  • 3. Choi YS, Choi SW, Yi JW. Prospective analysis of TERT promoter mutations in papillary thyroid carcinoma at a single institution. J Clin Med 2021;10:2179.ArticlePubMedPMC
  • 4. Lee J, Ha EJ, Roh J, Kim HK. Presence of TERT±BRAF V600E mutation is not a risk factor for the clinical management of patients with papillary thyroid microcarcinoma. Surgery 2021;170:743–7.ArticlePubMed
  • 5. Bae JS, Kim Y, Jeon S, Kim SH, Kim TJ, Lee S, et al. Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. Diagn Pathol 2016;11:21.ArticlePubMedPMC

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    Citations to this article as recorded by  
    • 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
      Young Joo Park, Eun Kyung Lee, Young Shin Song, Soo Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung
      International Journal of Thyroidology.2023; 16(1): 1.     CrossRef


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