Do BRAFV600E mutation and sodium-iodide symporter expression affect the response to radioactive iodine therapy in patients with papillary thyroid carcinoma?

Objective: To report on the associations between BRAF and sodium iodide symporter expressions and treatment outcomes in patients with papillary thyroid carcinoma.

Methods: Inclusion criteria included a pathologic diagnosis of papillary thyroid carcinoma of any stage, thyroidectomy followed by radioactive iodine therapy, and follow-up for at least 12 months after initial therapy. Events were classified as persistent or recurrent disease based on a clinical or investigational evidence of disease within or after, respectively, 1 year from initial therapy. Disease-free survival was calculated between the dates of surgery and confirmed event. Patients with no evidence of disease were censored at their last follow-up (censored group). BRAF mutation and sodium-iodide symporter expressions were evaluated using immunohistochemistry.

Results: The study included 78 patients (60 females, 18 males) with median age 36 years (range: 20-70 years). BRAF was positive in 78%, equivocal in 13%, and negative in 9%. Sodium-iodide symporter was positive in 88%. BRAF mutation was significantly associated with increasing tumor size, presence of lymphovascular invasion, classic subtype of papillary thyroid carcinoma, thyroid capsular infiltration, and lymph node metastasis. Sodium-iodide symporter expression was not associated with any clinical or pathologic characteristics. Patients with negative or equivocal BRAF had significantly better disease-free survival (82%, 3 events) compared to the positive group (41%, 33 events; P=0.02).

Conclusion: In patients with papillary thyroid carcinoma, BRAF mutation is associated with high-risk pathological characteristics and worsened disease-free survival.