Meckbach, Diana, Bauer, Jürgen, Pflugfelder, Annette, Meier, Friedegund, Busch, Christian, Eigentler, Thomas K., Capper, David, Mittelbronn, Michel, Von Deimling, Andreas, Perner, Sven, Ikenberg, Kristian, Hantschke, Markus, Büttner, Petra, Garbe, Claus, and Weide, Benjamin (2014) Survival according to BRAF-V600 tumor mutations - An analysis of 437 patients with primary melanoma. PLoS ONE, 9 (1). e86194. pp. 1-10.

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Abstract

The prognostic impact of BRAF-V600 tumor mutations in stage I/II melanoma patients has not yet been analyzed in detail. We investigated primary tumors of 437 patients diagnosed between 1989 and 2006 by Sanger sequencing. Mutations were detected in 38.7% of patients and were associated with age, histological subtype as well as mitotic rate. The mutational rate was 36.7% in patients with disease-free course and 51.7% in those with subsequent distant metastasis (p = 0.031). No difference in overall survival (p = 0.119) but a trend for worse distant-metastasis-free survival (p = 0.061) was observed in BRAF mutant compared to BRAF wild-type patients. Independent prognostic factors for overall survival were tumor thickness, mitotic rate and ulceration. An interesting significant prognostic impact was observed in patients with tumor thickness of 1 mm or less, with the mutation present in 6 of 7 patients dying from melanoma. In conclusion, no significant survival differences were found according to BRAF-V600 tumor mutations in patients with primary melanoma but an increasing impact of the mutational status was observed in the subgroup of patients with tumor thickness of 1 mm or less. A potential role of the mutational status as a prognostic factor especially in this subgroup needs to be investigated in larger studies.

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