Prognostic implications of the BRAF-V600E mutation in papillary thyroid carcinoma based on a new cut-off age stratification.

Gan X1, Shen F1, Deng X1, Feng J1, Lu J2, Cai W1, Peng L3, Zheng W1, Wang W1, Huang P1, Chen Z4, Guo M1, Xu B1.

Author information

1: Department of Thyroid Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
2: Department of Colorectal and Anal Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
3: Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong 518101, P.R. China.
4: Department of Thyroid Surgery, Guangzhou First People's Hospital, Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.

Abstract

The BRAF-V600E mutation is the most common and specific oncogenic event known in papillary thyroid carcinoma (PTC). However, it remains controversial whether there is an association between the BRAF-V600E mutation and clinicopathologically aggressive characteristics of PTC. The purpose of the present retrospective study was to investigate the significance of the BRAF-V600E mutation in predicting prognostic and aggressive clinicopathological characteristics according to a new age-based stratification. Clinical data and the BRAF-V600E mutation status of 475 patients with PTC were downloaded from The Cancer Genome Atlas database. The association between BRAF-V600E status and clinicopathological characteristics was analyzed by χ2 test or Fisher's exact test. Recurrence-free survival rate (RFS) was analyzed using the Kaplan-Meier method. Aggressive clinicopathological factors associated with recurrence were analyzed by Cox multivariate regression. This study was conducted on 219 cases of patients with PTC with a known BRAF-V600E mutational status. In the ≥55 years age group, BRAF-V600E was found to be significantly associated with aggressive PTC characteristics, including tumor size, PTC subtype, radioactive iodine (RAI) dose, follow-up time, recurrence, recurrence risk stage, advanced T stage, advanced N stage and American Joint Committee on Cancer (III/IV) stage (all P<0.05). RFS was analyzed by the log-rank test and exhibited statistically significant differences in the ≥55 years group (P=0.041), but there was no significant difference in the <55 group (P=0.757), according to the BRAF-V600E mutation status. The BRAF-V600E gene was excluded from the recurrence Cox multivariate regression model. The BRAF-V600E mutation was found to better predict aggressive and recurrent PTC based on age stratification with the cut-off age of 55 years. The synergistic interaction between BRAF-V600E mutation and the new age stratification may help clinicians reach the optimal decision in terms of surgical approach and the extent of surgery.