NRAS (Q61R), BRAF (V600E) immunohistochemistry: a concomitant tool for mutation screening in melanomas.

Arnaud Uguen 1, 2, 3 Matthieu Talagas 4, 1, 3 Sebastian Costa 1 Laura Samaison 4, 1, 3 Laure Paule 5 Zarrin Alavi 6 Marc De Braekeleer 4, 7, 3 Cédric Le Marechal 2, 3, 5, * Pascale Marcorelles 4, 1, 3, *
* Auteur correspondant
1 CHU - AnaPath - CHRU Brest - Laboratoire d'Anatomo-Pathologie
2 Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
3 UEB - Université européenne de Bretagne
4 LNB - Laboratoire de Neurosciences de Brest
5 Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest]
6 CIC 1412 - BREST - Centre d'Investigation Clinique INSERM 1412
7 Laboratoire de cytogénétique [Brest]
Abstract : 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. 142 formalin-fixed paraffin-embedded melanoma samples from 79 patients were analyzed using pyrosequencing and immunohistochemistry. 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. 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.
Keywords : Melanoma BRAF NRAS Molecular analysis Immunohistochemistry
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Article dans une revue
Diagnostic Pathology, BioMed Central, 2014, 10, pp.121. 〈10.1186/s13000-015-0359-0〉
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http://hal.univ-brest.fr/hal-01276448
Contributeur : Ghislaine Calvez <>
Soumis le : vendredi 19 février 2016 - 13:51:30
Dernière modification le : mardi 30 janvier 2018 - 10:42:01

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Arnaud Uguen, Matthieu Talagas, Sebastian Costa, Laura Samaison, Laure Paule, et al.. NRAS (Q61R), BRAF (V600E) immunohistochemistry: a concomitant tool for mutation screening in melanomas.. Diagnostic Pathology, BioMed Central, 2014, 10, pp.121. 〈10.1186/s13000-015-0359-0〉. 〈hal-01276448〉

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