Differential clinical associations of BRAF and NRAS mutations among histologic types of cutaneous melanomas.

Melanoma/Skin Cancers
Session Type and Session Title: 
This abstract will not be presented at the 2013 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr e20034)
David Stockman, Michael T. Tetzlaff, Tariq Al-Zaid, Carlos A. Torres-Cabala, Amanda Dawn Bucheit, Alexander J. F. Lazar, Dawen Sui, John Andrew Jakob, Roland Bassett, Victor G. Prieto, Michael A. Davies, Jonathan L. Curry; The University of Texas MD Anderson Cancer Center, Houston, TX; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX

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Abstract Disclosures


Background: Previous studies have investigated whether BRAF and NRAS mutation status in melanoma correlate with histologic parameters and overall survival (OS), but evaluation of mutation groups irrespective of specific mutation among histologic types of melanoma has led to variability in the reproducibility of results. We tested the hypothesis that different histologic types of melanoma (nodular [NM] and superficial spreading [SSM]) have distinct clinical associations with specific BRAF and NRAS mutations. Methods: Primary tumor histology, BRAF/NRAS mutation status, and clinical outcomes were collected for 195 patients (pts) with stage III or IV disease. Clinical associations with specific mutations were determined separately for patients with NM (n=105) and SSM (n=90) histologic types of primary cutaneous melanomas. Results: Mutational status in NM: 69 BRAF (66%), 19 NRAS (18%), & 17 wild-type (WT;16%). Specific BRAF mutations in NM: V600E 50 (75%), V600K 13 (19%), V600R 4 (6%). Specific NRAS mutations in NM: Q61K 6 (32%), Q61L 2 (11%), Q61R 8 (42%); other 3 (16%). Mutation status in SSM: 45 BRAF (50%), 24 NRAS (27%), 21 WT (23%). Specific BRAF mutations in SSM: V600E 32 (71%), V600K 12 (24%), V600R 0. Specific NRAS mutations in SSM: Q61K 2 (8%), Q61L 5 (21%), Q61R 12 (50%). The distribution of specific BRAF (p=0.21) and NRAS (p=0.29) mutations between NM and SSM was not significantly different. Among NM pts, pts with activating NRAS mutations had shorter OS from the diagnosis of Stage IV melanoma than WT (HR 3.42, p=0.02) and BRAF (HR 2.40, p=0.009). There was no significant difference for BRAF pts vs WT (HR 1.43, p=0.47). Among SSM patients, neither NRAS (HR 1.3, p=0.53) nor BRAF(HR 0.54, p=0.16) were significantly associated with OS compared to WT. Comparison of patients with BRAF V600E vs V600K showed significant association for OS from stage 4 in SSM pts (HR 0.24, p=0.01), but not in NM pts (HR 0.64, p=0.36). Conclusions: The prognostic significance of BRAF and NRAS mutations on OS from stage IV differed for pts with NM and SSM primaries. Further investigation of the histologic types of melanoma with specific BRAF and NRAS mutations in a larger series is necessary to validate these apparent impacts on patient outcomes.