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Open Access 01-10-2013 | Research Paper

Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma

Authors: Einar Birkeland, Christian Busch, Elisabet Ognedal Berge, Jürgen Geisler, Göran Jönsson, Johan Richard Lillehaug, Stian Knappskog, Per Eystein Lønning

Published in: Clinical & Experimental Metastasis | Issue 7/2013

Abstract

Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and <0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma.

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Title: Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma
Authors: Einar Birkeland
Christian Busch
Elisabet Ognedal Berge
Jürgen Geisler
Göran Jönsson
Johan Richard Lillehaug
Stian Knappskog
Per Eystein Lønning
Publication date: 01-10-2013
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 7/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-013-9587-4

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