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BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis.
MedLine Citation:
PMID:  22859608     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Langerhans-cell histiocytosis (LCH) is a clinically and histologically heterogeneous disorder. Its classification as either reactive inflammatory or neoplastic has been a matter of debate. However, the recent finding of frequent BRAFV600E mutations in LCH argues for the latter. The exact cell type which harbours the mutation and is responsible for proliferation remains to be identified. We here apply a BRAFV600E mutation specific antibody to detect the BRAF mutant cells in lesions from 89 patients with LCH. We found BRAFV600E mutations in 34/89 (38%) lesions. In lesions with the BRAFV600E mutation, the vast majority of cells co-expressing S-100 and CD1a harboured mutant BRAFV600E protein. These cells also expressed CD14 and CD36 while varying fractions exhibited CD207. On the other hand, CD80 and CD86 expression was also present on BRAFV600E positive cells. Thus, cells of variable maturation, exhibiting an immunohistochemical profile compatible either with myeloid cell or with de-differentiated Langerhans cell antigens, carry the BRAFV600E mutation. In conclusion, we identify and characterize the neoplastic cells in LCH with BRAFV600E mutations by applying a mutation specific marker and demonstrate feasibility for routine screening.
Authors:
Felix Sahm; David Capper; Matthias Preusser; Jochen Meyer; Albrecht Stenzinger; Felix Lasitschka; Anna-Sophie Berghoff; Antje Habel; Marion Schneider; Andreas Kulozik; Ioannis Anagnostopoulos; Leonhard Müllauer; Gunhild Mechtersheimer; Andreas von Deimling
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-2
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universitaet Heidelberg, Heidelberg, Germany;
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