Survival according to BRAF-V600 tumor mutations--an analysis of 437 patients with primary melanoma.
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.
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Diana
D
Meckbach
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Jürgen
J
Bauer
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Annette
A
Pflugfelder
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Friedegund
F
Meier
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Christian
C
Busch
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Thomas K
TK
Eigentler
German Cancer Research Center (DKFZ), Heidelberg, Germany ; Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
David
D
Capper
German Cancer Research Center (DKFZ), Heidelberg, Germany ; Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
Andreas
A
von Deimling
Edinger Institute, Institute of Neurology, Goethe University, Frankfurt, Germany.
Michel
M
Mittelbronn
Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
Sven
S
Perner
Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
Kristian
K
Ikenberg
Dermatopathology Friedrichshafen, Friedrichshafen, Germany.
Markus
M
Hantschke
Skin Cancer Research Group, School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Australia.
Petra
P
Büttner
Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
Claus
C
Garbe
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.
Benjamin
B
Weide
D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012042:Registries; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
D048493:Proto-Oncogene Proteins B-raf