Intra-and inter-tumor braf heterogeneity in acral melanoma: An immunohistochemical analysis

Takamichi Ito, Yumiko Kaku-Ito, Maho Murata, Toshio Ichiki, Yuki Kuma, Yuka Tanaka, Taketoshi Ide, Fumitaka Ohno, Maiko Wada-Ohno, Yuichi Yamada, Yoshinao Oda, Masutaka Furue

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15 Citations (Scopus)


The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma—a distinct type of melanoma with a unique genetic background—has not fully been investigated. We conducted a retrospective review of our acral melanoma patients. Of the 196 patients with acral melanoma, we retrieved 31 pairs of primary and matched metastatic melanomas. We immunostained the 31 pairs with VE1, a BRAFV600E-mutation-specific monoclonal antibody. Immunohistochemistry with VE1 showed a high degree of sensitivity and specificity for detecting BRAFV600E mutations compared with the real-time polymerase chain reaction method. A total of nine primary (29.0%) and eight metastatic (25.8%) acral melanomas were positive for VE1. In three patients (9.7%), we observed a discordance of VE1 staining between the primary and metastatic lesions. Of note, VE1 immunohistochemical staining revealed a remarkable degree of intra-tumor genetic heterogeneity in acral melanoma. Our study reveals that VE1 immunostaining is a useful ancillary method for detecting BRAFV600E mutations in acral melanoma and allows for a clear visualization of intra-and inter-tumor BRAF heterogeneity.

Original languageEnglish
Article number6191
JournalInternational journal of molecular sciences
Issue number24
Publication statusPublished - Dec 2 2019

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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