Dual NRASQ61R and BRAFV600E mutation-specific immunohistochemistry completes molecular screening in melanoma samples in a routine practice

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• 作者：Arnaud Uguen ; MD^a ; ^b ; ^c ; ^{arnaud.uguen@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Paul Gué ; guen ; MD^a ; ^c ; ^d ; ^{paul.gueguen@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Delphine Legoupil ; MD^e ; Sté ; phanie Bouvier^b ; ^{stephanie.bouvier4@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Sebastian Costa ; MD^b ; ^{sebastian.costa@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Sandrine Duigou^b ; ^{sandrine.duigou@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Gilles Lemasson ; MD^b ; ^{gilles.lemasson@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Franç ; oise Ledé ; MD^b ; ^{francoise.lede@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Bruno Sassolas ; MD^f ; ^{bruno.sassolas@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Matthieu Talagas ; MD^b ; ^c ; ^g ; ^{matthieu.talagas@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Claude Fé ; rec ; MD ; PhD^a ; ^c ; ^d ; ^{claude.ferec@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Cé ; dric Le Maré ; chal ; MD ; PhD^a ; ^c ; ^d ; ^{cedric.lemarechal@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Marc De Braekeleer ; MD ; PhD^a ; ^c ; ^h ; ^{marc.debraekeleer@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author} ; Pascale Marcorelles ; MD ; PhD^b ; ^c ; ^g ; ^{pascale.marcorelles@chu-brest.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Melanoma ; BRAF ; NRAS ; Immunohistochemistry ; Molecular analysis
• 刊名：Human Pathology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：46
• 期：11
• 页码：1582-1591
• 全文大小：964 K

文摘

NRAS and BRAF mutational status has become mandatory to treat patients with metastatic melanomas. Mutation-specific immunohistochemistry (IHC) can help analyze challenging tumor samples. We report our experience integrating NRASQ61R (SP174) and BRAFV600E (VE1) IHC in routine practice in a cancer molecular genetic platform. All samples screened for BRAF and NRAS mutations during the year 2014 were analyzed by IHC and pyrosequencing, with an independent analysis of the 2 methods. Cases with first-line discordant results benefited from a complementary second-round IHC and next-generation sequencing (NGS) with a final interpretation taking into account the results of pyrosequencing, IHC, NGS, and quantification of the tumor cells. We analyzed 111 consecutive formalin-fixed and paraffin-embedded melanoma samples from 101 patients. Twenty-two and 11 samples were concordant for BRAFV600E and NRASQ61R mutations, respectively. Second-round analyses of 9 discordant and 1 molecularly inconclusive samples allowed conclusion in 4 further mutated samples (2 BRAFV600E and 2 NRASQ61R). A sample remained NRASQ61R IHC negative but NRASQ61R mutated with molecular methods. Overall, BRAFV600 and NRASQ61 mutation frequencies were 31.7% and 30.7%, respectively. When compared to molecular results, the sensitivity and specificity of IHC were 100% for BRAFV600E IHC and 92.3% and 98.9% for NRASQ61R IHC, respectively. IHC interpretation required a more stringent cutoff for BRAFV600E IHC than NRASQ61R to minimize false results. We conclude that NRASQ61R and BRAFV600E IHC coupled with NGS allow detection of mutations in melanoma challenging samples.