American Surgical Association
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The Prevalence and Prognostic Value of BRAF Mutation In Thyroid Cancer
Electron Kebebew*, Julie Weng*, Orlo H Clark, Quan Duh, Juergen Bauer*, Boris Bastian*, Gustavo Ranvier*
University of California, San Francisco, San Francisco, CA


OBJECTIVE(S): To examine the prevalence of BRAF mutation among thyroid cancer histologic subtypes and define the association of BRAF mutation with poor prognostic indicators of papillary thyroid cancer.
SUMMARY BACKGROUND DATA: The appropriate extent of surgical treatment, adjuvant therapy and follow-up for thyroid cancer remains controversial. Advances in the molecular biology of thyroid cancer have helped identify candidate markers of disease aggressiveness. A common genetic alteration found is a point mutation in the BRAF oncogene (BRAF V600E), which might be present almost exclusively in papillary thyroid cancer and is associated with more aggressive disease.
METHODS: BRAF mutation status was determined in tumor samples from 318 patients with thyroid cancer [218 classic papillary thyroid cancer (PTC), 73 follicular thyroid cancer, and 26 follicular variant of papillary thyroid cancer (FVPTC)]. Data on clinicopathologic characteristics and clinical course were collected prospectively.
RESULTS: The prevalence of BRAF V600E mutation was higher in classic PTC (52.3%) than in FVPTC (19.2%) and FTC (1.4%) (p < 0.0001). BRAF V600E mutation was significantly associated with lymph node metastasis (p = 0.0323), distant metastasis (p = 0.045), and higher TNM stage (I and II vs. III and IV, p = 0.0047), and with a higher rate of recurrent and persistent disease in patients with PTC (p = 0.0389) after a median follow-up time of 5.7 years.
CONCLUSIONS: BRAF V600E mutation is almost exclusively present in classic PTC and is associated with aggressive disease at presentation. Testing for this mutation may be useful for selecting initial therapy and follow-up.

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