Predictors of BRAF Mutation in Melanocytic Nevi: Analysis across Regions with Different UV Radiation Exposure
Sarah Karram, Asif Loya, Suad Taraif, Christian Oberkanins, Ibrahim Khalifeh. American University of Beirut Medical Center, Beirut, Lebanon; ViennaLab Diagnostics GmbH, Vienna, Austria; Shaukat Khanum Memorial Cancer Center, Lahore, Pakistan; SAAD Specialist Center, Al Khobar, Saudi Arabia
Background: BRAF mutations have been implicated in initiating pro-mutagenic cellular proliferation mostly based on homogeneous Western cohorts. Data addressing the possible interaction between exposure to different solar UV radiation (UVR) magnitudes and BRAF mutation rate (BMR) in Melanocytic Nevi (MN) are limited.
Design: Extended BRAF testing for 9 mutations in 225 MN cases derived from 215 patients from 4 different UVR regions: Lebanon (n=95; 110 kJ/m2/year), Syria (n=23; 93.5 kJ/m2/year), Saudi Arabia (n=70; 139kJ/m2/year) and Pakistan (n=37; 118kJ/m2/year) was performed. Data collected included: age, gender, anatomic location and lesion size. Histologic parameters recorded were: MN type [junctional (JN), compound (CMN), intradermal (IDN), blue (BN), cellular blue (CBN), compound spitz (CSN) and intradermal spitz (ISN), congenital (CN)], solar elastosis grade and nevus pigmentation degree. Cumulative 21-year UVR averages were derived from The National Center for Atmospheric Research.
Results: BRAF mutation status was obtained in 210 cases (6.7% failed PCR). Overall BMR was 62.4% (131/210) with V600E mutation accounting for 98.5% of cases. Discordant mutation status was found in 2/10 patients with multiple nevi. BMR differed significantly, yet non-systematically, among UVR regions (fig.1 left). Mutation rates varied widely across MN type (fig.1 middle; p<0.001) and by anatomic location (fig.1 right; p<0.001). Severe pigmentation was less frequent in BRAF mutation positive nevi [5/131 (4%) vs. 34/79 (43%); p<0.001]. Multivariate independent predictors of BRAF mutation in MN were: age [OR (95% C.I.) = 1.43 (1.13-1.74) per 10 years; p=0.004], anatomic location [p=0.043 overall] and nevus type [p<0.001 overall]. UVR region was not an independent predictor of BRAF mutation.
Conclusions: Increased BRAF mutation with age along with the lack of a UVR magnitude - BRAF mutation association suggests that duration of exposure rather than UVR exposure dose is the more likely link to acquiring the mutation. Our results also point to a possible protective role of increased pigmentation against acquiring BRAF mutation.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 73, Monday Morning