Clinicopathological significance of TERT promoter mutation in papillary thyroid carcinomas: a systematic review and meta-analysis

6588 Background: Co-existing of BRAF V600E and TERT promoter C228T/C250T mutation has been extensively related to prognosis in thyroid cancer. Our study aimed to establish a more sensitive method for mutation detection and explore the correlation more in-depth. Methods: BRAF and TERT promoter mutation status of 250 papillary thyroid cancer was detected by both Amplification Refractory Mutation System quantitative PCR (ARMS-qPCR) and Sanger sequencing to compare the sensitivity. The associations between the mutation status and the clinicopathological features were analyzed. Results: ARMS-qPCR displayed higher sensitivity than Sanger ( BRAF V600E: 75.2% vs. 52.4%, p< 0.001; TERT promoter C228T/C250T: 12.0% vs. 3.6%, p= 0.001; Co-mutation (9.6% vs. 3.2%, p= 0.005). Both methods indicated that patients with BRAF V600E and TERT promoter co-mutation were higher in age at diagnosis (ARMS-qPCR: 51.0 ± 14.2 vs. 40.2 ± 12.6, p <0.001; Sanger: 64.3 ± 7.1 vs. 40.5 ± 12.6, p <0.001), and the recurrence rate (16.7% vs. 3.1%, p= 0.014; 50.0% vs. 2.9%, p< 0.001), besides, the co-mutation group were related to more advanced TNM stage ( p< 0.001; p< 0.001) and higher MACIS score (5.1 ± 1.5 vs. 4.2 ± 0.7, p= 0.006; 6.6 ± 1.1 vs. 4.2 ± 0.8, p< 0.001). In addition, compared with the co-mutation results of Sanger, it seems that ARMS-qPCR has identified an earlier stage of group, which were younger (43.3 ± 10.1 vs. 66.4 ± 6.1, p< 0.001), and with smaller tumor (1.8 ± 1.5 vs. 4.0 ± 1.3, p= 0.002), as well as lower recurrence rate ( 0.0% vs. 50%, p= 0.007). Besides, the newly identified group were lower in MACIS score (4.2 ± 0.8 vs. 6.9 ± 0.7, p= 0.002) and with lower TNM stage ( p= 0.001). Conclusions: Patients with BRAF V600E and TERT promoter C228T/C250T co-mutation have a worse prognosis. Using ARMS-qPCR, the more sensitive method could identify earlier stages of patients with a potentially worse prognosis. [Table: see text]

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Prospective Analysis of TERT Promoter Mutations in Papillary Thyroid Carcinoma at a Single Institution

Journal of Clinical Medicine ◽

10.3390/jcm10102179 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2179

Author(s):

Yun-Suk Choi ◽

Seong-Woon Choi ◽

Jin-Wook Yi

Keyword(s):

Thyroid Cancer ◽

Surgical Margin ◽

Tert Promoter Mutation ◽

Papillary Thyroid ◽

Brafv600e Mutation ◽

Promoter Mutation ◽

Large Tumor ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

Background: Papillary thyroid cancer (PTC) has the highest cancer incidence in Korea. It is known that some thyroid cancers have aggressive clinical behavior and a poor prognosis. Genomic studies have described some somatic mutations that are related to the aggressive features of thyroid cancer, such as the BRAFV600E mutation. Recently, TERT promoter mutations were identified and reported as poor prognostic factors in PTC. Our aim was to identify the frequency and clinical impact of TERT promoter mutation in PTC. Methods: Analysis of both BRAFV600E and TERT promoter mutations in thyroidectomy specimens began in February 2019. As of December 2020, 622 patients had been tested. Data were prospectively collected and retrospectively reviewed to ascertain clinical and pathologic variables. Results: TERT promoter mutations were identified in 13 patients (2.09%); 12 had the C228T mutation, and one had the C216T mutation. In total, ten patients had the BRAFV600E mutation. TERT promoter mutation was significantly associated with advanced age (46.795 ± 12.616 versus 65.692 ± 13.628 years, p < 0.001), large tumor size (1.006 ± 0.829 versus 2.285 ± 1.938 cm, p = 0.035), extrathyroidal extension, surgical margin involvement, angioinvasion, BRAFV600E mutation and advanced TNM stage, a higher MACIS score and a high proportion of radioactive iodine therapy application. Logistic regression showed that lymphatic and angioinvasion and BRAFV600E mutation were predictive of TERT promoter mutation. Conclusions: Our study is the first to report the prospective results of TERT promoter mutations at a single tertiary hospital in Incheon, Korea. PTC with TERT promoter mutation was associated with more aggressive behavior than PTC with wild-type TERT gene status.

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