Concern regarding the presence of intertumoral heterogeneity of BRAF mutation status in patients with metastatic
melanoma has led to uncertainty surrounding which specimens should preferentially undergo BRAF testing. We sought to examine the extent of intrapatient heterogeneity of BRAF(V600E)
protein expression in patients with multiple
tumors. Sixty-four patients with 171
tumors at various stages of
disease progression had
tumor BRAF(V600E)
protein expression immunohistochemically (IHC) assessed using the BRAF(V600E) mutant-specific antibody VE1.
Melanoma sections were examined for staining intensity (score 0 to 3), the presence of intratumoral heterogeneity, and concordance with molecular BRAF genotype. Intrapatient, intertumoral heterogeneity of BRAF(V600E) expression was also assessed by comparing VE1 staining on different
tumors within the same patient. All specimens from 64 patients displayed complete intertumoral homogeneity of BRAF(V600E) expression status, and all
tumors had concordant molecular and IHC BRAF status. Only 1 patient demonstrated >1 level of staining intensity heterogeneity between specimens. Intratumoral heterogeneity of staining intensity was not observed in any specimen. IHC-measured BRAF(V600E)
protein expression displays complete intertumoral homogeneity, minimal intertumoral intensity heterogeneity, and no intratumoral heterogeneity in metastatic
melanoma patients in various stages of
disease progression. Our results suggest that, provided there is adequate quantity of viable
tumor cells and minimal admixture of nontumor cells, testing any
melanoma sample from a patient with metastatic disease will accurately determine BRAF status for treatment planning.