Abstract
BRAFV600E mutation has been related to tumor aggressiveness and patients prognostic. However, the role of BRAF gene expression, as an important MAPK pathway activator, and its relationship to patients outcome are still poorly understood. BRAF expression quantified by real-time PCR was compared to clinical data regarding diagnosis (age, sex, environmental and tobacco exposure, size and pre operative ultrasound features), type of surgery, post-op complications, histological criteria of aggressiveness, and outcome of 63 PTC patients (6 men and 57 women, 47±13.9 years old) followed up for 5 to 56 months (21.4±12.45 months) using a standard protocol. Forty five were classic PTC; 11 were follicular variants and 7 presented other variants. Eighteen measured less than 1 centimeter; 9=1-2 cm; 35= 2-4 cm and 1 had more than 4cm. Forty two patients were classified as stage I; 10=stage II; 9=stage III and 2=stage IV. BRAF quantitative expression was classified from 1 to 10 arbitrary units (AU). Patients were divided in group A (mild BRAF expression= 1 to 5 AU), B (medium BRAF expression= 5 to 10 AU¬) and C (BRAF hyperexpression > 10AU). The overall survival was 83.3% in 48 months. Five cases had local recurrence (7.9%) and one patient presented a distant metastasis during the follow up (1.5%). Two patients died of the disease (3.1%). Multivariate analysis showed that tobacco smoking (p<0.0001); lymph node metastasis (p=0.035); completion of surgery (p=0.03) and the rate of post-operatory complications (p=0.02) influenced disease-free and overall survival. Univariate analysis showed that BRAF gene expression (p=0.01); histological criteria of aggressiveness (p><0, 0001); sex (p=0.01); tumor size (p=0.002) and tumor extension (p=0.016) were determinants of bad prognosis. We concluded that the quantification of BRAF expression, together with other classical criteria of prognostic, may help sort out patients of higher risk.