Clinical Correlates of Specific BRAF and NRAS Mutations in Melanoma
Erica E Syklawer, John Jakob, Roland L Bassett, Jeffrey E Gershenwald, Victor G Prieto, Jonathan L Curry, Michael A Davies, Alexander J Lazar. University of Texas Health Science Center at Houston, Houston, TX; The University of Texas MD Anderson Cancer Center, Houston, TX
Background: The treatment of melanoma is rapidly evolving due to an improved understanding of the molecular heterogeneity of this disease. While previous studies have identified differences between melanomas with activating BRAF and NRAS mutations, there is minimal information regarding characteristics that correlate with specific mutations of these genes.
Design: We reviewed the results of CLIA-certified molecular testing for BRAF and NRAS mutations performed, primarily using metastatic disease, on melanoma patients (pts) from 2/2007 to 9/2010. Pts with the following mutations were identified (n=437) for study: (1) BRAF V600E & V600K; (2) NRAS exon 1 (G12/G13) & exon 2 (Q60/Q61). Demographics (age, sex), primary tumor characteristics (subtype, location, histology, Breslow thickness, mitotic rate, ulceration), and characteristics at stage IV disease (age, BMI, serum LDH, involved sites, M category) were tabulated. The time from initial diagnosis to stage IV and overall survival (OS) were determined. Comparisons between mutation groups used Fisher's exact test for categorical variables and t-tests for continuous parameters. Kaplan-Meier (KM) analysis estimated the distribution of time to event endpoints; distribution comparisons used the log-rank test.
Results: Identified pts (n=437) with mutations were: BRAF V600E (n=230); BRAF V600K (n=72); NRAS exon 2 (n=111); NRAS exon 1 (n=24). Among pts with BRAF mutations, compared to V600K, V600E was associated with younger age (p<0.0001), female sex (p=0.001), primary tumor location (p=0.008), and longer interval from primary diagnosis to stage IV disease (p=0.01). Among pts with stage IV disease, V600K pts trended toward inferior OS among those who received treatment with a BRAF or MEK inhibitor (p=0.28) and those who did not (p=0.21), but statistical significance was not reached. Comparison of pts with NRAS exon 1 and exon 2 mutations identified significant associations with primary tumor location (p=0.0004) and histologic subtype (p=0.02). No other significant associations were identified.
Conclusions: Significant associations with pt demographics and primary tumor characteristics were identified with specific BRAF and NRAS mutations. As delivery of precision treatment and prognosis are increasingly guided by molecular features in melanoma, pathologists must remain fully cognizant of the clinical implications of molecular testing.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 105, Wednesday Afternoon