BRAF Mutational Epidemiology in Dysplastic Nevi: Does Different Solar UV Radiation Exposure Matter?
Maya Saroufim, Suad Taraif, Asif Loya, Christian Oberkanins, Ibrahim Khalifeh. American University of Beirut Medical Center, Beirut, Lebanon; SAAD Specialist Center, Al Khobar, Saudi Arabia; Shaukat Khanum Memorial Cancer Center, Lahore, Pakistan; ViennaLab Diagnostics GmbH, Vienna, Austria
Background: BRAF mutation rates have been reported in nevi and melanomas of homogeneous Caucasian cohorts. However, the demographics of BRAF mutations in dysplastic nevi (DN) of populations with differing solar UV radiation (UVR) exposure have not been investigated.
Design: Extended BRAF testing for 9 mutations in DN (n=125) from 101 patients derived from populations with differing UVR rates: 1) Lebanon (LB, n=68): UVR=110 kJ/m2/yr and Saudi Arabia (SA, n=57): UVR= 139 kJ/m2/yr was performed. Clinical data collected included age, sex, anatomic location and size. Histologic parameters including architectural and cytological features, as reported by Shea et al., in addition to solar elastosis grade, were recorded. Cumulative averages of UVR over a 21 year period were derived from The National Center for Atmospheric Research databases.
Results: BRAF mutation status (BMS) was obtained for 113 of 125 (9.6%; 12 failed PCR) cases resulting in an overall mutation rate of 63/113(55.8%). BRAF mutation rate differed significantly by UVR regions (LB 53.4%, SA 74.4%, p<0.05). V600E was the prominent mutation in 61/63 (96.8%) cases. A 6/15 (40%) discordant mutation rate was found in patients with multiple nevi examined including 2 patients with different mutation types. Histologic examination subdivided the dysplasia as follows; mild (n=24), moderate (n=60) and severe (n=41) with trunk predominance (72.8%). Higher rates of pigment in stratum corneum were identified in SA (p<0.05). The frequency of BRAF mutation showed marginal significant increase with advanced architectural and cytological atypia. Intermittent sun damage and compound nevus type were significant predictors of positive BMS (p<0.05). The histologic parameters predictive of negative BMS included upper extremity location, regression, cohesiveness and suprabasal melanocytes (p<0.05). Positive BMS was reasonably predicted by multivariate binary logistic regression [C-statistic (95% (C.I.)) = 0.72 (0.62-0.83)] by 2 independent predictors: 1) Geographic location [OR (95% C.I.) = 2.87 (1.14-7.21); p=0.025] and 2) Compound nevus type [OR (95% C.I.) = 4.52 (1.85-11.04); p=0.025].
Conclusions: In the Near Eastern cohort, there is a significant increase in DN BRAF mutation rate at higher UVR exposures supporting a role for UVR in promoting BRAF mutation. In patients with multiple DN examined, discordant BMS negates an underlying constitutional predilection.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 76, Monday Morning