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PLoS One. 2014 Jan 24;9(1):e86194. doi: 10.1371/journal.pone.0086194. eCollection 2014.

Survival according to BRAF-V600 tumor mutations--an analysis of 437 patients with primary melanoma.

Author information

1
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
2
German Cancer Research Center (DKFZ), Heidelberg, Germany ; Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
3
Edinger Institute, Institute of Neurology, Goethe University, Frankfurt, Germany.
4
Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
5
Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
6
Dermatopathology Friedrichshafen, Friedrichshafen, Germany.
7
Skin Cancer Research Group, School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Australia.
8
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany ; German Cancer Research Center (DKFZ), Heidelberg, Germany ; German Cancer Consortium (DKTK), Heidelberg, Germany.

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.

PMID:
24475086
PMCID:
PMC3901680
DOI:
10.1371/journal.pone.0086194
[Indexed for MEDLINE]
Free PMC Article

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