Clinical Aspects of Braf Mutation in Thyroid Cancer

The BRAF mutation has been extensively studied in recent years in thyroid cancer, particularly for its aggressive role and clinical potential in papillary thyroid cancer (PTC). This mutation is the most common known genetic alteration in PTC, seen in 45% of cases on average, with a lower prevalence in low-stage disease. The mutation causes a change in amino acid at position 600 from valine to glutamic acid in the BRAF protein kinase, constitutively activating it and resulting in aberrant activation of the MAP kinase signaling pathway. Most of the studies have shown a strong association of BRAF mutation with aggressive clinicopathological outcomes of PTC, including tumor extrathyroidal extension, lymph node metastasis, advanced TNM stages, loss of radioiodine avidity, disease persistence/recurrence, and even patient death. The aggressive role of BRAF mutation has also been demonstrated in low-stage and micro-PTC. This mutation is therefore generally viewed as a strong prognostic molecular marker for poorer prognosis of PTC. The BRAF mutation can be tested for on thyroid fine needle aspiration biopsy specimens to assist diagnostic evaluation of thyroid nodules and preoperative risk stratification of PTC. Information from such testing can be helpful in guiding early decision making on surgical and medical treatments of thyroid nodules and PTC. The BRAF mutant has also been demonstrated to be an effective therapeutic target in thyroid cancer. Use of BRAF mutation as a diagnostic and prognostic molecular marker as well as a therapeutic target has shown an increasing impact on our current management of thyroid cancer.