Activating BRAF V600E mutation in aggressive pediatric Langerhans cell histiocytosis: Demonstration by allele-specific PCR/direct sequencing and immunohistochemistry

Gábor Méhes, Gábor Irsai, Judit Bedekovics, Lívia Beke, Ferenc Fazakas, Tímea Rózsa, Csongor Kiss

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Langerhans cell histiocytosis (LCH) is a rare neoplastic disease originating from cells characterized by antigenpresenting Langerhans cell phenotype. The clinical spectrum of LCH is highly variable including localized and disseminated forms mostly occurring in children. Recently, about 60% of LCHs were reported to carry the activating BRAF mutation V600E. In our retrospective study, we evaluated the occurrence and prognostic impact of the V600E mutation in formaldehydefixed, paraffin-embedded samples from 15 pediatric LCH cases treated at our institution. Allele-specific polymerase chain reaction (PCR) and direct sequencing were used to demonstrate the presence of V600E mutation, and immunohistochemistry (IHC) using the mutant protein-specific VE1 antibody clone was performed to confirm mutant BRAF protein expression. Eight of 15 (53.3%) cases proved to be BRAF mutants by any of the methods applied, with a single case showing a discrepancy (PCR negative/IHC positive). Four of the BRAF-mutant cases (50.0%) showed refractory disease and progressed to death within 43 months, whereas the remaining mutant cases were stable and responded well to therapy. Wild-type BRAF cases (7/15, 46.6%) with generally comparable initial presentation were all treated successfully. In conclusion, activating V600E BRAF mutation can be frequently demonstrated in pediatric LCH by both allele-specific PCR and IHC. Unfavorable risk cases potentially also responding to BRAF-inhibitory therapy can be identified by mutation testing using archival formaldehydefixed, paraffin-embedded tumor samples.

Original languageEnglish
Pages (from-to)1644-1648
Number of pages5
JournalAmerican Journal of Surgical Pathology
Volume38
Issue number12
DOIs
Publication statusPublished - Jan 1 2014

Keywords

  • BRAF mutation
  • Childhood cancer
  • Histiocytosis
  • Molecular pathology
  • Prognosis
  • Vemurafenib

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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