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

Abstract:

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.

journal_name

Arch Pathol Lab Med

authors

Marin C,Beauchet A,Capper D,Zimmermann U,Julié C,Ilie M,Saiag P,von Deimling A,Hofman P,Emile JF

doi

10.5858/arpa.2013-0031-OA

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

71-5

issue

1

eissn

0003-9985

issn

1543-2165

journal_volume

138

pub_type

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