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Open Access 01-12-2015 | Research

NRAS ^Q61R, BRAF ^V600E immunohistochemistry: a concomitant tool for mutation screening in melanomas

Authors: Arnaud Uguen, Matthieu Talagas, Sebastian Costa, Laura Samaison, Laure Paule, Zarrin Alavi, Marc De Braekeleer, Cédric Le Marechal, Pascale Marcorelles

Published in: Diagnostic Pathology | Issue 1/2015

Abstract

Background

The determination of NRAS and BRAF mutation status is a major requirement in the treatment of patients with metastatic melanoma. Mutation specific antibodies against NRAS^Q61R and BRAF^V600E proteins could offer additional data on tumor heterogeneity. The specificity and sensitivity of NRAS^Q61R immunohistochemistry have recently been reported excellent. We aimed to determine the utility of immunohistochemistry using SP174 anti-NRAS^Q61R and VE1 anti-BRAF^V600E antibodies in the theranostic mutation screening of melanomas.

Methods

142 formalin-fixed paraffin-embedded melanoma samples from 79 patients were analyzed using pyrosequencing and immunohistochemistry.

Results

23 and 26 patients were concluded to have a NRAS-mutated or a BRAF-mutated melanoma respectively. The 23 NRAS ^Q61R and 23 BRAF ^V600E-mutant samples with pyrosequencing were all positive in immunohistochemistry with SP174 antibody and VE1 antibody respectively, without any false negative. Proportions and intensities of staining were varied. Other NRAS ^Q61L , NRAS ^Q61K , BRAF ^V600K and BRAF ^V600R mutants were negative in immunohistochemistry. 6 single cases were immunostained but identified as wild-type using pyrosequencing (1 with SP174 and 5 with VE1). 4/38 patients with multiple samples presented molecular discordant data. Technical limitations are discussed to explain those discrepancies. Anyway we could not rule out real tumor heterogeneity.

Conclusions

In our study, we showed that combining immunohistochemistry analysis targeting NRAS^Q61R and BRAF^V600E proteins with molecular analysis was a reliable theranostic tool to face challenging samples of melanoma.

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Title: NRAS Q61R , BRAF V600E immunohistochemistry: a concomitant tool for mutation screening in melanomas
Authors: Arnaud Uguen
Matthieu Talagas
Sebastian Costa
Laura Samaison
Laure Paule
Zarrin Alavi
Marc De Braekeleer
Cédric Le Marechal
Pascale Marcorelles
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-015-0359-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

NRAS ^Q61R, BRAF ^V600E immunohistochemistry: a concomitant tool for mutation screening in melanomas

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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