BACKGROUND: To examine the association between level and patterns of baseline 
intra-tumoural BRAF(V600E) protein expression and clinical outcome of 
BRAF(V600E) melanoma patients treated with selective BRAF inhibitors.
METHODS: Fifty-eight BRAF(V600E) metastatic melanoma patients treated with 
dabrafenib or vemurafenib on clinical trials had pre-treatment tumour 
BRAF(V600E) protein expression immunohistochemically (IHC) assessed using the 
BRAF V600E mutant-specific antibody VE1. Sections were examined for staining 
intensity (score 1-3) and percentage of immunoreactive tumour cells, and from 
this an immunoreactive score (IRS) was derived (intensity × per cent 
positive/10). The presence of intra-tumoural heterogeneity for BRAF(V600E) 
protein expression was also assessed. BRAF(V600E) expression was correlated with 
RECIST response, time to best response (TTBR), progression-free survival (PFS) 
and overall survival (OS).
RESULTS: Expression was generally high (median IRS 28 (range 5-30)) and 
homogeneous (78%). Expression of mutated protein BRAF(V600E) as measured by 
intensity, per cent immunoreactive cells, or IRS did not correlate with RECIST 
response, TTBR, PFS or OS, including on multivariate analysis. Heterogeneity of 
staining was seen in 22% of cases and did not correlate with outcome.
CONCLUSION: In the current study population, IHC-measured pre-treatment 
BRAF(V600E) protein expression does not predict response or outcome to BRAF 
inhibitor therapy in BRAF(V600E) metastatic melanoma patients.