Funding sources Canadian Institutes of Health Research (MOP-93810 and MOP-110974) and Canadian Dermatology Foundation (G.L.); Canadian Institute of Health Research – Skin Research Training Centre Trainee Award (G.S.A., S.M.J.); Roman M. Babicki Fellowship and University of British Columbia Graduate Fellowship (S.M.J.).
Clinical and Laboratory Investigations
Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma
Article first published online: 13 AUG 2013
© 2013 The Authors BJD © 2013 British Association of Dermatologists
British Journal of Dermatology
Volume 169, Issue 2, pages 320–328, August 2013
How to Cite
Safaee Ardekani, G., Jafarnejad, S.M., Khosravi, S., Martinka, M., Ho, V. and Li, G. (2013), Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma. British Journal of Dermatology, 169: 320–328. doi: 10.1111/bjd.12351
Conflicts of interest None declared.
- Issue published online: 13 AUG 2013
- Article first published online: 13 AUG 2013
- Accepted manuscript online: 1 APR 2013 09:47AM EST
- Manuscript Accepted: 25 MAR 2013
Mutation of BRAF is a prevalent event in melanoma. Despite much attention to the role of BRAF mutation in melanoma, the status of BRAF protein expression and its significance in melanoma progression are unknown.
We investigated the BRAF expression level in different stages of melanocytic lesions and evaluated its correlation with clinicopathological features and patient survival.
Using tissue microarray, BRAF expression and its correlation with patient outcome was evaluated in 49 naevi samples and 370 patients with melanoma. We also evaluated the correlation of BRAF protein expression and V600E mutation using direct sequencing.
Compared with naevi samples, BRAF expression was remarkably increased in primary melanomas and further increased in metastatic melanomas (P = 1·8 × 10−11). High BRAF expression was significantly correlated with thicker tumours, ulceration and higher American Joint Committee on Cancer stages (P = 1·5 × 10−7, 1·5 × 10−5 and 3·6 × 10−13, respectively). In cases of primary melanoma, patients with high BRAF expression had significantly worse overall (P = 0·009) and disease-specific 5-year survival (P = 0·007). While there was a trend for higher prevalence of BRAF V600E mutation in patients with high BRAF protein expression, no significant correlation was observed between protein expression and BRAF mutation. Furthermore, univariate Cox regression analysis confirmed high BRAF protein expression as a strong risk factor for poor patient survival in primary melanoma [hazard ratio (HR) 2·08 for overall survival; HR 2·39 for disease-specific survival].
Our data demonstrate that BRAF protein expression is significantly increased during melanoma progression. In addition, we revealed a novel prognostic value for BRAF protein expression in primary melanoma as it is significantly correlated with poor patient survival.