Association between BRAF V600E mutation and recurrence of papillary thyroid cancer

Abstract

Purpose: To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC).

Patients and methods: This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months).

Results: The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation-positive and 11.6% (125 of 1,082) of BRAF V600E mutation-negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation-positive versus -negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation-positive versus -negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories.

Conclusion: This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2014 by American Society of Clinical Oncology.

Figures

Fig 1.

Kaplan-Meier survival curves of effect of BRAF V600E mutation status on disease recurrence–free probability in patients with various types of papillary thyroid cancer (PTC). Comparison of recurrence-free survival of patients, represented by indicated log-rank and P values in each panel, was performed between BRAF V600E–negative and –positive groups for (A) all patients, (B) those with conventional PTC, and (C) those with follicular-variant PTC. Follow-up time truncated at 15 years.

Fig 2.

Kaplan-Meier survival curves of interaction of BRAF V600E mutation with clinicopathologic risk factors in affecting disease-free probability in patients with papillary thyroid cancer (all types). (A) Lymph node metastasis (LNM) and BRAF V600E mutation, (B) tumor extrathyroidal extension (EXT) and BRAF V600E mutation, and (C) patients age ≥ 60 years and BRAF V600E mutation. In each panel, P values were from log-rank tests, adjusted for multiple comparisons, comparing each stratum with patients negative for both BRAF V600E mutation and indicated clinicopathologic factor. Follow-up time truncated at 15 years.