title: Application of a BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia.
abstract: In recent times BRAF V600E mutations have emerged as a genetic hallmark of hairy cell leukemia (HCL). This specific point mutation is present in virtually all cases of HCL but is exceedingly rare in other peripheral B-cell neoplasms. In this study we investigated the application of a BRAF V600E mutation-specific antibody (clone VE1) to differentiate HCL from HCL mimics, such as HCL variant and splenic marginal zone lymphoma. A total of 52 routinely processed formalin-fixed paraffin-embedded tissue specimens were investigated (bone marrow, n=46; spleen, n=6) for expression of V600E-mutated BRAF protein. All 32 cases of HCL were scored positive, and all non-HCL cases were scored negative. In 28 of 30 HCL cases the presence of a BRAF V600E mutation could be confirmed by direct sequencing, whereas no BRAF mutations were detected among 20 HCL mimics. We further screened 228 mature B-cell neoplasms with VE1 and detected 1 positive case of chronic lymphocytic leukemia. Sequencing confirmed the presence of a BRAF V600E mutation. In conclusion, we demonstrate that VE1 immunohistochemistry can be used to reliably differentiate HCL from HCL-mimicking entities. This on-slide technique might be particularly helpful in interpreting challenging biopsies with low tumor content.
authors.affiliation: Department of General Pathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Andrulis
authors.forename: Roland
authors.initials: R
authors.lastname: Penzel
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: David
authors.initials: D
authors.lastname: Capper
mesh_terms: D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D001706:Biopsy; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D007943:Leukemia, Hairy Cell / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017354:Point Mutation; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis* / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf