Prognostic and predictive values of oncogenic BRAF, NRAS, c‐KIT and MITF in cutaneous and mucous melanoma. (26th January 2015)

• Record Type: Journal Article
• Authors: Pracht, M.; Mogha, A.; Lespagnol, A.; Fautrel, A.; Mouchet, N.; Le Gall, F.; Paumier, V.; Lefeuvre‐Plesse, C.; Rioux‐Leclerc, N.; Mosser, J.; Oger, E.; Adamski, H.; Galibert, M.‐D.; Lesimple, T.
• Is Part Of: Journal of the European Academy of Dermatology and Venereology. Volume 29:Number 8(2015:Aug.)
• Page Start: 1530
• Page End: 1538
• Publication Date: 2015-01-26
• Subjects: Dermatology -- Periodicals; Sexually transmitted diseases -- Periodicals; 616.5
• DOI: 10.1111/jdv.12910
• Languages: English
• ISSNs: 0926-9959

Abstract

<abstract abstract-type="main" id="jdv12910-abs-0001"> <title>Abstract</title> <sec id="jdv12910-sec-0001" sec-type="section"> <title>Background</title> <p>Mutations of <italic>BRAF, NRAS and c‐KIT</italic> oncogenes are preferentially described in certain histological subtypes of melanoma and linked to specific histopathological features. BRAF‐, MEK‐ and KIT‐inhibitors led to improvement in overall survival of patients harbouring mutated metastatic melanoma.</p> </sec> <sec id="jdv12910-sec-0002" sec-type="section"> <title>Objectives</title> <p>To assess the prevalence and types of <italic>BRAF, NRAS, c‐KIT</italic> and <italic>MITF</italic> mutations in cutaneous and mucous melanoma and to correlate mutation status with clinicopathological features and outcome.</p> </sec> <sec id="jdv12910-sec-0003" sec-type="section"> <title>Methods</title> <p>Clinicopathological features and mutation status of 108 samples and of 98 consecutive patients were, respectively, assessed in one retrospective and one prospective study. Clinicopathological features were correlated with mutation status and the predictive value of these mutations was studied.</p> </sec> <sec id="jdv12910-sec-0004" sec-type="section"> <title>Results</title> <p>This work identified significant correlations between <italic>BRAF</italic> mutations and melanoma occurring on non‐chronic sun‐damaged skin and superficial spreading melanoma (<italic>P</italic> < 0.05) on one hand, and between NRAS mutations and nodular melanoma (<italic>P</italic> < 0.05) on the other hand. Younger age (<italic>P</italic> < 0.05), microscopic (<italic>P</italic> < 0.05) and macroscopic (<italic>P</italic> < 0.05) lymphatic involvement at diagnosis of primary melanoma were significantly linked to <italic>BRAF</italic> mutations. A mutated status was a positive predictive factor of a response to <italic>BRAF</italic> inhibitors (OR = 3.44). Mutated melanoma showed a significantly (<italic>P</italic> = 0.038) higher objective response rate to cytotoxic chemotherapy (26.3%) than wild‐type tumours (6.7%).</p> </sec> <sec id="jdv12910-sec-0005" sec-type="section"> <title>Conclusion</title> <p>Clinical and pathological characteristics of the primary melanoma differed between wild‐type and <italic>BRAF‐</italic> or <italic>NRAS</italic>‐mutated tumours. Patients with <italic>BRAF</italic>‐mutated tumours were younger at diagnosis of primary melanoma. Patients carrying mutations showed better responses better to specific kinase inhibitors and interestingly also to systemic cytotoxic chemotherapy.</p> </sec> </abstract>