Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Sep;41(9):724-32.
doi: 10.1111/cup.12364. Epub 2014 Jul 4.

Validation of the VE1 immunostain for the BRAF V600E mutation in melanoma

Michelle V Pearlstein  1 , Daniel C Zedek, David W Ollila, Amanda Treece, Margaret L Gulley, Pamela A Groben, Nancy E Thomas
Affiliations

Validation of the VE1 immunostain for the BRAF V600E mutation in melanoma

Michelle V Pearlstein et al. J Cutan Pathol. 2014 Sep.

Abstract

Background: BRAF mutation status, and therefore eligibility for BRAF inhibitors, is currently determined by sequencing methods. We assessed the validity of VE1, a monoclonal antibody against the BRAF V600E mutant protein, in the detection of mutant BRAF V600E melanomas as classified by DNA pyrosequencing.

Methods: The cases were 76 metastatic melanoma patients with only one known primary melanoma who had had BRAF codon 600 pyrosequencing of either their primary (n = 19), metastatic (n = 57) melanoma, or both (n = 17). All melanomas (n = 93) were immunostained with the BRAF VE1 antibody using a red detection system. The staining intensity of these specimens was scored from 0 to 3+ by a dermatopathologist. Scores of 0 and 1+ were considered as negative staining while scores of 2+ and 3+ were considered positive.

Results: The VE1 antibody showed a sensitivity of 85% and a specificity of 100% as compared to DNA pyrosequencing results. There was 100% concordance between VE1 immunostaining of primary and metastatic melanomas from the same patient. V600K, V600Q, and V600R BRAF melanomas did not positively stain with VE1.

Conclusions: This hospital-based study finds high sensitivity and specificity for the BRAF VE1 immunostain in comparison to pyrosequencing in detection of BRAF V600E in melanomas.

Keywords: dermatopathology; immunohistochemistry; melanoma.

PubMed Disclaimer

Figures

Figure 1
Figure 1
BRAF wild type melanoma in a lymph node that is negative for VE1 immunostain alongside a 3+ positive capsular melanocytic nevus (Original magnification ×100).
Figure 2
Figure 2
BRAF wild type melanoma with 1+ weak cytoplasmic and nuclear blush on VE1 immunostain (Original magnification ×200).
Figure 3
Figure 3
A, BRAF V600E mutant primary melanoma with positive staining for VE1 (×200). B, Corresponding BRAF V600E metastatic melanoma with positive staining for VE1 in the same patient (Original magnification ×100).
Figure 3
Figure 3
A, BRAF V600E mutant primary melanoma with positive staining for VE1 (×200). B, Corresponding BRAF V600E metastatic melanoma with positive staining for VE1 in the same patient (Original magnification ×100).
See this image and copyright information in PMC

References

    1. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–954. - PubMed
    1. Nissan MH, Solit DB. The "SWOT" of BRAF Inhibition in Melanoma: RAF Inhibitors, MEK Inhibitors or Both? Current Oncology Reports. 2011;13:479–487. - PubMed
    1. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nature Genetics. 2003;33:19–20. - PubMed
    1. Forbes SA, Bindal N, Bamford S, Cole C, Kok CY, Beare D, et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Research. 2011;39:D945–D950. - PMC - PubMed
    1. Busca R, Abbe P, Mantoux F, Aberdam E, Peyssonnaux C, Eychene A, et al. Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes. Embo Journal. 2000;19:2900–2910. - PMC - PubMed

Publication types