Reassessing the Role of BRAF p.V600E in Papillary Thyroid Cancer

Nicole A. Cipriani, MD, surgical pathologist at the University of Chicago Medicine, addresses the clinical relevance of the BRAF p.V600E mutation in risk stratification for patients with papillary thyroid carcinoma (PTC), offering insights from a recent study published in Endocrine Pathology.

According to Cipriani, while the BRAF p.V600E mutation has historically garnered attention for its potential role in prognostication, recent evidence suggests it may have limited utility in stratifying risk for patients with PTC in the modern clinical landscape. Specifically, in the “post-NIFTP era” (non-invasive follicular thyroid neoplasm with papillary-like nuclear features), the mutation does not appear to significantly inform management decisions.

“Based on this study, we believe that BRAF p. V600E in risk stratifying papillary thyroid carcinomas in the sort of post NIFTP era is actually not very useful, so we would not alter our management based on BRAF expression,” she explains in an interview with Targeted Oncology^TM.

Despite its limited role in determining prognosis, the mutation retains strong relevance for potential therapeutic targeting. Cipriani emphasizes that identifying BRAF p.V600E remains important for future treatment decisions, especially in patients with high-grade, aggressive, or radioactive iodine–refractory disease. In such cases, BRAF-targeted therapies, including BRAF inhibitors and combination regimens, may offer significant clinical benefit.

“[It is] still important for potential treatment, but maybe less important as a prognosticator in and of itself,” she adds.

The study she referenced, published by Brumfield et al. in Endocrine Pathology (2025), evaluated the prevalence and clinical impact of the BRAF p.V600E mutation in a large cohort of patients with PTC. While mutation prevalence was confirmed, its independent prognostic value was limited when adjusted for other clinicopathologic factors.

REFERENCE:

Brumfield A, Azar SA, Nordgren R, et al. Prevalence and Clinical Impact of BRAF p.V600E Mutation in Papillary Thyroid Carcinoma. Endocr Pathol. 2025;36(1):13. Published 2025 Apr 16. doi:10.1007/s12022-025-09859-y