BRAF V600E protein expression and outcome from BRAF inhibitor treatment in BRAF V600E metastatic melanoma

摘要

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 x 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.