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Detection of BRAF p.V600E Mutations in Melanoma by Immunohistochemistry Has a Good Interobserver Reproducibility

2013; American Medical Association; Volume: 138; Issue: 1 Linguagem: Inglês

10.5858/arpa.2013-0031-oa

1543-2165

Cristi Marin, Alain Beauchet, David Capper, U. Zimmermann, Catherine Julié, Marius Ilié, Philippe Saïag, Andreas von Deimling, Paul Hofman, Jean‐François Emile,

HER2/EGFR in Cancer Research

Context.—Assessment of BRAF p.V600E mutational status has become necessary for treatment of patients with metastatic melanoma. Detection of p.V600E mutation by immunohistochemistry was recently reported in several tumor types.Objective.—To evaluate the interobserver reproducibility of BRAF p.V600E detection by immunohistochemistry in melanoma.Design.—Immunohistochemistry with VE1 antibody was performed on metastatic melanomas of 67 patients. Staining interpretation was performed on digital image virtual slides of tissue microarrays. The p.V600E status was determined by 7 pathologists from 3 European laboratories, blinded for other interpretations and for molecular biology results.Results.—Melanomas had p.V600E (n = 30), p.V600K (n = 4), p.K601E (n = 1), p.600–601delinsE (n = 1), or no p.V600 mutations (n = 31). Staining of p.V600E within mutated cells was cytoplasmic and diffuse, and for each case the staining on the 3 tissue microarray cores was similar. In 53 cases (79.1%) the 7 pathologists had perfect concordance. Agreement of interobserver reproducibility was almost perfect (κ = 0.81 [0.77–0.85]). Only 2 false-positive responses (0.9%) were obtained. The specificities reported were 100% for 5 pathologists (two of whom previously trained for p.V600E interpretation), and 97% for 2 untrained pathologists.Conclusions.—Detection of BRAF p.V600E mutation by immunohistochemistry in melanomas has an excellent interobserver reproducibility. Our results suggest that immunohistochemistry could be used as a first step for detection of BRAF p.V600E mutation, to identify patients with melanoma as candidates for BRAF inhibitors.