Fudan University Shanghai Cancer Center, Shanghai, China
Peng-cheng Yu , Li-cheng Tan , Xiao Shi , Ben Ma , Wen-jun Wei , Yu Wang , Qing-hai Ji , Yu-long Wang
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.
ARMS-qPCR Co-Mut | p | Sanger Co-Mut | p | ARMS-qPCR(+) | p | ||||
---|---|---|---|---|---|---|---|---|---|
+(n = 24) | -(n = 226) | + (n = 8) | - (n = 242) | Sanger + (n = 8) | Sanger-, (n = 16) | ||||
Age at diagnosis ± SD | 51.0±14.2 | 40.2±12.6 | < 0.001 | 66.4±6.1 | 40.4±12.5 | < 0.001 | 66.4±6.1 | 43.3±10.1 | < 0.001 |
Size(cm) ± SD | 2.5±1.8 | 1.8±1.0 | 0.057 | 4.0±1.8 | 1.8±1.0 | < 0.001 | 4.0±1.3 | 1.8 ±1.5 | 0.002 |
Recurrence, n (%) | 4(16.7) | 7(3.1) | 0.014 | 4(50.0) | 7(2.9) | < 0.001 | 4(50.0) | 0(0.0) | 0.007 |
MACIS score ± SD | 5.1±1.5 | 4.2±0.7 | 0.006 | 6.9±0.7 | 4.2±0.8 | < 0.001 | 6.9±0.7 | 4.2±0.8 | < 0.001 |
TNM stage, n (%) | < 0.001 | < 0.001 | 0.001 | ||||||
I+II | 23(95.8) | 225(99.5) | 7(87.5) | 241(99.6) | 6(87.5) | 17(100.0) | |||
III+IV | 1(4.2) | 1(0.4) | 1(12.5) | 1(0.4) | 1(12.5) | 0(0.0) |
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2021 ASCO Annual Meeting
First Author: Giuseppe Lombardi
2023 ASCO Annual Meeting
First Author: Kai Ou
2016 ASCO Annual Meeting
First Author: Gregory Chang
2023 ASCO Annual Meeting
First Author: Eiji Oki