Immunohistochemical BRAF V600E expression and intratumor BRAF V600E heterogeneity in acral melanoma: Implication in melanoma-specific survival

Abstract

Acral melanoma, a distinct form of cutaneous melanoma originating in the glabrous skin of the palms, soles, and nail beds, has a different genetic background from other subtypes of cutaneous melanoma. The roles of oncogenic BRAF mutations of acral melanoma in pathogenesis and patient outcomes have not been fully elucidated. We retrieved a total of 112 patients with primary acral melanoma and checked their BRAF V600E status using immunohistochemical staining of VE1 antibody. Among these cases, 21 acral melanoma samples (18.8%) showed positive BRAF V600E staining, and of those, 11 samples (9.8%) showed a heterogeneous staining pattern, with a mixture of VE1-positive and VE1-negative cells. BRAF V600E positivity was significantly associated with thicker melanoma (p = 0.0015). There was no significant difference in clinicopathological factors between homogeneous and heterogeneous VE1-positive acral melanoma. Both patients with BRAF V600E-positive acral melanoma and those with heterogeneous BRAF V600E had significantly shorter melanoma-specific survival than those with BRAF V600E-negative melanoma in Kaplan–Meier analysis (p = 0.0283 and p = 0.0065, respectively). These findings provide novel insights into the pathobiology of acral melanoma.