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      Prospective immunohistochemical analysis of BRAF V600E mutation in melanoma.

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          Abstract

          The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation is the most common activating genetic alteration of this oncogene and a predictive marker for the therapeutic use of BRAF inhibitors in melanoma. Our aim was to evaluate the performance of BRAF V600E mutation-specific monoclonal antibody (VE1) in a prospective diagnostic setting of melanoma patients (n = 102). All 41 cases (40.2%) that showed a V600E mutation in the cyclic minisequencing analysis of the DNA were also initially scored immunopositive. Two cases that were scored as BRAF V600E mutation positive by immunohistochemistry were negative in the DNA-based mutation analysis and determined to be immunonegative in a repeated staining with more representative specimens. Thus, BRAF V600E mutation detection using immunohistochemistry was 100% sensitive and 96.8% specific, when compared with the analysis of the DNA. None of the BRAF V600K mutations was detected by the VE1 antibody (n = 7). However, the VE1 antibody detected a rare V600E2 mutation. We also studied the role of BRAF V600E mutation in a set of melanoma patients who had been investigated for sentinel node metastasis. Melanoma lymph node metastases were diagnosed in 21.8% (12/55) of the sentinel nodes, and BRAF V600E immunopositivity was detected in 34.5% (19/55) of the cases. BRAF V600E mutation status did not correlate with any clinicopathological parameters. In conclusion, analysis of BRAF V600E mutation in melanoma by immunohistochemistry is a sensitive and specific method, which can be used to identify BRAF inhibitor-sensitive melanoma patients as a first-line method due to its rapid and affordable nature.

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          Author and article information

          Journal
          Hum. Pathol.
          Human pathology
          1532-8392
          0046-8177
          Feb 2015
          : 46
          : 2
          Affiliations
          [1 ] Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital, 00029 Helsinki, Finland; University of Helsinki, 00014 Helsinki, Finland; Genome-Scale Biology, Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland.
          [2 ] Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital, 00029 Helsinki, Finland; University of Helsinki, 00014 Helsinki, Finland.
          [3 ] Laboratory of Genetics, HUSLAB, Helsinki University Central Hospital, HUSLAB, 00029 Helsinki, Finland.
          [4 ] Department of Plastic Surgery, Helsinki University Central Hospital, 00029 Helsinki, Finland.
          [5 ] Department of Oncology, Helsinki University Central Hospital, 00029 Helsinki, Finland.
          [6 ] Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Central Hospital, 00029 Helsinki, Finland; University of Helsinki, 00014 Helsinki, Finland; Genome-Scale Biology, Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland. Electronic address: ari.ristimaki@helsinki.fi.
          Article
          S0046-8177(14)00432-8
          10.1016/j.humpath.2014.08.018
          25442222
          98135af9-3df9-4784-9005-a45b7f3aeeb2
          Copyright © 2015 Elsevier Inc. All rights reserved.
          History

          BRAF,Macrophages,Melanoma,Pigment,Prospective,Sentinel node,V600
          BRAF, Macrophages, Melanoma, Pigment, Prospective, Sentinel node, V600

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