Intra- and Inter-Tumoral Homogeneity of BRAFV600E Mutations in Melanoma Tumors

The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAF(V600) inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAF(V600) mutations. Although the BRAF(V600E) mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAF(V600E) heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAF(V600E) expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAF(V600E) expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAF(V600E) VE1 antibody for the detection of BRAF(V600E) mutations in melanoma tumors.