<b>Objective:</b> The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAFV600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma.
BRAF mutation examined in FNAB specimens, compared with the wild-type allele, strongly predicted perithyroidal invasion (48 vs. 29%; P = 0.017), extracapsular spread (65 vs. 45%; P = 0.017), occult central lymph node metastasis (35 vs. 15%; P = 0.004), and advanced TNM stage (44 vs. 28%; P = 0.035).
BRAF(V600E) mutation-positive cancers (55.3%) were more frequently associated with lymph node metastasis (p=0.01) and advanced TNM stage (III-IV) (p=0.03).
BRAFV600E mutation status was not associated with clinicopathologic characteristics of aggressive behavior such as extrathyroidal extension, lymph node metastases, higher T-categories, male sex, and greater age.
BRAF mutation was associated with lymph node metastasis (adjusted RRR 2.46 95% CI 1.07-5.69, P=0.04) and sentinel lymph node positivity (adjusted odds ratio [aOR] OR 1.55, 95% CI 1.14-2.10, P=0.005).
Additional genotyping of PTC cases for the BRAFV600E mutation revealed for the first time a close relation between SLP-2 overexpression and the presence of BRAF mutation (p = 0.02) with high positive rates of lymph node metastasis (70%) and extrathyroid invasion (80%) in these cases.
Additionally, there were significant associations (P<0.05) between BRAF(V600E) and a higher tumor-node-metastasis staging (III/IV), and between miR-21* over-expression and lymph node metastasis.
Association of BRAFV600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers.