BRAF V600E mutation in papillary thyroid cancer is correlated with adverse clinicopathological features but not with iodine exposure.

INTRODUCTION: BRAFV600E activating mutation is the most frequent genetic abnormality in the pathogenesis of papillary thyroid carcinoma. We aimed to evaluate the association between BRAFV600E mutation and well-established prognostic clinicopathological characteristics as well as iodine exposure. MATERIAL AND METHODS: From 2000 to 2012, the data of PTC patients admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital in Turkey were reviewed retrospectively. Clinicopathological parameters were collected. BRAFV600E mutation was analysed by DNA sequencing method in tumour specimens. We hypothesised thatBRAFV600E mutation prevalence is positively correlated with prolonged iodine exposure and expected to be higher in the second half of the recruitment period due to the increment in time spent from the iodisation process of the table salt in our country. Thus, iodine exposure was categorised as short-term (2000-2006) and long-term (2006-2012). RESULTS: A total of 197 patients were accrued. The study population predominantly consisted of conventional variant. A statistically significant relationship was observed betweenBRAFV600E mutation presence and age (p = 0.03), conventional variant PTC (p = 0.00002), T4 stage (p = 0.002), vascular invasion (p = 0.036), thyroid capsule invasion (p < 0.00001), extrathyroidal tissue invasion (p < 0.00001), and lymph node metastasis (p < 0.00001). When categorised as long-term and short-term, iodine exposure was not statistically significantly related withBRAFV600E mutation; however, there were far more PTC cases in the long-term group (86.3% vs. 13.7%). CONCLUSION: We revealed that BRAFV600E mutation is associated with adverse clinicopathological parameters. There appeared to be no relation between long-term iodine exposure and BRAFV600E.

Radiotherapy utilization in BRAF mutation-tested metastatic melanoma in the targeted therapy era.

AIM: Tumor BRAF mutation testing is routine for all patients with metastatic melanoma (MM) owing to the availability of agents targeting this intracellular pathway. To test whether there is a difference in radiotherapy (RT) utilization according to BRAF mutation status, we performed a retrospective review of RT utilization in a contemporary cohort undergoing BRAF mutation testing. METHODS: Clinical records of MM patients undergoing BRAF mutation testing between April 2010 and August 2012 were reviewed. Overall survival (OS) was calculated using Kaplan-Meier methods. Differences between BRAF status were calculated using chi-square tests for categorical variables, median tests for continuous variables and Cox proportional hazards models to compare OS. RESULTS: Up to 158 patients were identified but 17 were excluded due to inadequate clinical data. Of the remaining 141 patients, 69 (49%) tested BRAF mutant (BRAF-m), median age 47 years (range 21-79) with median follow-up of 16.8 months (IQR11.3-25.2). Seventy-two (51%) tested BRAF wild type (BRAF-w), median age 62 years (range 25-84) with median follow-up of 27.1 months (IQR12.5-57.4). Overall, RT utilization was similar: 68% in BRAF-m and 69% in BRAF-w. Mean number of treatment courses was 1.70 for BRAF-m and 2.36 for BRAF-w (Pearson chi-square 3.92, P = 0.05). Up to 51% of BRAF-m and 56% of BRAF-w required ≧2 RT courses. Forty-six percent BRAF-m compared with 29% BRAF-w received brain RT (P = 0.04). Median OS was 17.7 months (IQR7.6-35.5) in BRAF-m and 19 months (IQR7.8-35.1) in BRAF-w (P = 0.99). CONCLUSION: High RT utilization rates were observed irrespective of BRAF mutation status. Significantly more BRAF-w patients received RT but more BRAF-m patients received brain RT.

Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site.

A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk signal transduction pathway. Consistent data demonstrate the early appearance, in a mutually exclusive manner, of these mutations. The purpose of this paper is to summarize the literature on NRAS and BRAF activating mutations in melanoma tumors with respect to available data on histogenetic classification as well as body site and presumed UV-exposure. Common alterations of the signal transducing network seem to represent molecular hallmarks of cutaneous melanomas and therefore should continue to strongly stimulate design and testing of targeted molecular interventions.