Clinical Significance of BRAF (V600E) Mutation and Ki-67 Labeling Index in Papillary Thyroid Carcinomas

Abstract

Background: Activating mutations of the BRAF gene have recently been reported in thyroid carcinomas. In particular, V600E mutation is highly prevalent in papillary thyroid carcinoma (PTC). Patients and Methods: In this study, the BRAF (V600E) mutation in 54 PTCs was investigated and the relationship between the BRAF mutation and clinicopathological features such as age, gender, tumor size, extrathyroid extension, lymph node metastasis, and distant metastasis was analyzed. Additionally, Ki-67 labeling index (LI) was determined to evaluate tumor cell proliferative activity. Results: The BRAF mutation was detected in 26 (65%) of 40 primary and 12 (85.7%) of 14 recurrent PTCs. The BRAF mutation was significantly related to older age (57.4 vs. 43.1 years, p=0.012), extrathyroid extension (76.9% vs. 35.7%, p=0.026), and lymph node metastasis (88.5% vs. 57.1%, p=0.044). Moreover, the mean Ki-67 LI was significantly higher in BRAF-positive patients than in BRAF-negative patients (1.01% vs. 0.135%, p=0.014). The BRAF mutation was common in PTCs classified as advanced TNM stage. Eighteen of 20 (90%) patients in TNM stages III and IV were positive for this gene mutation. Similarly, the BRAF mutation was investigated in 14 recurrent PTCs and was detected in 85.7% (12 of 14). The BRAF mutation was also common in patients with regional lymph node recurrence. Conclusion: These results suggest that PTCs with BRAF (V600E) mutation are more aggressive than those with wild-type BRAF. This mutation may be important for predicting a worse prognosis in patients with PTC.