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

Xiaoxiong Gan; Fei Shen; Xingyan Deng; Jianhua Feng; Jiabao Lu; Wensong Cai; Lina Peng; Weipeng Zheng; Weijia Wang; Peidan Huang; Zhen Chen; Mengli Guo; Bo Xu

doi:10.3892/ol.2019.11132

Prognostic implications of the BRAF-V600^E mutation in papillary thyroid carcinoma based on a new cut-off age stratification

Oncol Lett. 2020 Jan;19(1):631-640. doi: 10.3892/ol.2019.11132. Epub 2019 Nov 21.

Authors

Xiaoxiong Gan¹, Fei Shen¹, Xingyan Deng¹, Jianhua Feng¹, Jiabao Lu², Wensong Cai¹, Lina Peng³, Weipeng Zheng¹, Weijia Wang¹, Peidan Huang¹, Zhen Chen⁴, Mengli Guo¹, Bo Xu¹

Affiliations

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-V600^E 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-V600^E mutation and clinicopathologically aggressive characteristics of PTC. The purpose of the present retrospective study was to investigate the significance of the BRAF-V600^E mutation in predicting prognostic and aggressive clinicopathological characteristics according to a new age-based stratification. Clinical data and the BRAF-V600^E mutation status of 475 patients with PTC were downloaded from The Cancer Genome Atlas database. The association between BRAF-V600^E 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-V600^E mutational status. In the ≥55 years age group, BRAF-V600^E 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-V600^E mutation status. The BRAF-V600^E gene was excluded from the recurrence Cox multivariate regression model. The BRAF-V600^E 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-V600^E mutation and the new age stratification may help clinicians reach the optimal decision in terms of surgical approach and the extent of surgery.

Keywords: BRAF mutation; papillary thyroid carcinoma; prognosis; recurrence.