Combined BRAF V600E and TERT Promoter Mutations Identify Aggressive and Recurrent Papillary Thyroid Cancer
In a study reported in Journal of Clinical Oncology, Xing et al found that the combined presence of BRAF V600E and TERT C228T mutations was associated with increased risk of recurrence and poor disease-free survival in patients with papillary thyroid cancer.
The retrospective study included 365 women and 142 men with a mean age of 46 years. Median follow-up was 24 months.
Worse Clinicopathologic Features
Compared with patients with neither mutation, patients with BRAF V600E mutation alone had significantly greater tumor size and were at significantly greater risk for extrathyroidal invasion, lymph node metastasis, disease stage III/IV, and tumor recurrence. Those with TERT C228T alone were at significantly greater risk of lymph node metastasis. Patients with both mutations had significantly increased risk for virtually all classical high-risk characteristics and for metastatic recurrence.
Increased Recurrence Risk
Tumor recurrence rates were 25.8% (77.6/1,000 person-years) vs 9.6% (22.9/1,000 person-years) in patients with vs without BRAF V600E mutation (hazard ratio [HR] = 3.22, 95% confidence interval [CI]= 2.05–5.07) and 47.5% (108.5/1,000 person-years) vs 11.4% (30.2/1,000 person-years) in those with vs without TERT C228T mutation (HR = 3.46, 95% CI = 2.19–5.45). Recurrence rates were 68.6% (211.8/1,000 person-years) vs 8.7% (21.6/1,000 person-years) in patients with both mutations vs neither mutation (HR = 8.51, 95% CI = 4.84–14.97), with this difference remaining significant after adjustment for clinicopathologic factors.
Disease-free survival was significantly reduced in patients with vs without BRAF V600E mutation and with vs without TERT C228T mutation alone and in patients with both mutations vs neither mutation (P < .001 for all), with the survival curves for the latter groups diverging markedly more sharply than the curves for patents with vs without the individual mutations.
The investigators concluded, “Coexisting BRAF V600E and TERT C228T mutations form a novel genetic background that defines [papillary thyroid cancer] with the worst clinicopathologic outcomes, providing unique prognostic and therapeutic implications.
Mingzhao Xing, MD, PhD, of The Johns Hopkins University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the National Institutes of Health. Dr. Xing holds a U.S. patent related to BRAF mutation in thyroid carcinoma.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
