Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients

Abstract

Background: Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients. Methods: We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma. Results: Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences. Conclusion:This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

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 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][2][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.…”

“…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.…”

“…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.…”

Are TERT promoter mutations a poor prognostic factor in anaplastic thyroid carcinoma?

“…TERT promoter mutations have been identi ed in over 50 human cancers including thyroid cancer [4]. In meta-analysis, they were found in 10-20% of differentiated thyroid carcinoma (DTC) and 40% of poorly-differentiated thyroid carcinoma (PDTC) or anaplastic thyroid carcinoma (ATC) [5][6][7]. They are highly prevalent in large tumors, old age, aggressive histology, advanced stages, and distant metastasis [5,6].…”

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.)

“…We would like to thank Dr. Kim and colleagues for carefully reading our article and providing thoughtful comments regarding our recent publication, titled “Frequency of TERT promoter mutations in real-world analysis of 2,092 thyroid carcinoma patients” [ 1 ]. We reported that the frequency of real-world telomerase reverse transcriptase ( TERT ) promoter mutations in thyroid carcinoma was lower (3.4%) than in a previous report [ 2 ], and it was particularly low in papillary thyroid carcinoma (PTC) ≤1 cm (0.5%).…”