RET fusion rather than BRAF mutation confers a higher risk of aggressiveness and recurrence in papillary thyroid carcinoma.

BACKGROUND

BRAF mutation and RET fusion are the most common point mutation and rearrangement, respectively, in papillary thyroid carcinoma (PTC). However, the impact of BRAF mutation on PTC phenotype and recurrence and its relationship with RET fusion are not clearly defined. Therefore, the present study aims to analyze the relationships among BRAF mutation, RET fusion, and the aggressive phenotype of PTC.

METHODS

This single-center, real-world, retrospective study included 777 patients diagnosed with PTC who underwent initial surgical treatment and genetic testing at Sun Yat-sen University Cancer Center between July 2018 and October 2021.

RESULTS

A more aggressive phenotype, including advanced T and N stages, extranodal extension, and recurrence, was significantly more common in BRAF mutation-negative patients than in BRAF mutation-positive patients. KM survival analysis showed that patients with wild-type BRAF exhibited worse recurrence-free survival (RFS). Compared to RET fusion-negative patients, RET fusion-positive patients exhibited a higher prevalence of the aggressive phenotype and a lower RFS probability. In addition, the frequency of RET fusion was significantly higher in BRAF mutation-negative patients than in BRAF mutation-positive patients. Subgroup analysis, stratified by RET, revealed no significant differences in clinical variables between the BRAF wild-type and mutant cohorts. RFS rate between the BRAF mutation-negative and mutation-positive groups showed no significant differences within RET-stratified patient subgroups.

CONCLUSIONS

A mutually exclusive-like relationship exists between BRAF mutation and RET fusion in PTC. RET fusion appears to be more associated with the aggressive phenotype of PTC. However, further validation using a larger cohort of samples is warranted.