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American Journal of Surgical Pathology:
doi: 10.1097/PAS.0b013e31826485c0
Original Articles

Immunohistochemistry Is Highly Sensitive and Specific for the Detection of V600E BRAF Mutation in Melanoma

Long, Georgina V. MD, PhD, FRACP*,†,‡; Wilmott, James S. BSc*,§; Capper, David MD∥,¶; Preusser, Matthias MD∥,#; Zhang, Yuxiao E. MBiotech*; Thompson, John F. MD, FRACS, FACS*, **,††; Kefford, Richard F. MBBS, PhD, FRACP*,†,‡; von Deimling, Andreas MD∥,¶; Scolyer, Richard A. MD, FRCPA, FRCPath*,§,‡‡

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Abstract

This study investigated the sensitivity and specificity of immunohistochemical (IHC) analysis using an anti-BRAF antibody to detect the presence of the BRAF V600E mutation in patients with metastatic melanoma. A total of 100 patients with American Joint Committee on Cancer stage IIIC unresectable or stage IV melanoma and who underwent tumor DNA BRAF mutation testing were selected. Paraffin-embedded, formalin-fixed melanoma biopsies were analyzed for the BRAF mutation status by independent, blinded observers using both conventional DNA molecular techniques and IHC with the novel BRAF V600E mutant-specific antibody, VE1. The antibody had a sensitivity of 97% (37/38) and a specificity of 98% (58/59) for detecting the presence of a BRAF V600E mutation. Of the BRAF-mutated cases, none of the non-V600E cases (including V600K) stained positive with the antibody (0/11). There were 5 cases with discordant BRAF mutation results. Additional molecular analysis confirmed the immunohistochemically obtained BRAF result in 3 cases, suggesting that the initial molecular testing results were incorrect. Two of these patients would not have received a BRAF inhibitor on the basis of the initial false-negative mutation testing result. Two cases remained discordant. The reported IHC method is an accurate, rapid, and cost-effective method for detecting V600E BRAF mutations in melanoma patients. Clinical use of the V600E BRAF antibody should be a valuable supplement to conventional mutation testing and allow V600E mutant metastatic melanoma patients to be triaged rapidly into appropriate treatment pathways.

© 2013 Lippincott Williams & Wilkins, Inc.

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