A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma

Lo, Michelle; Paterson, Anna; Maraka, Jane; Clark, R.R.; Goodwill, Joseph; Nobes, Jenny; Garioch, J.; Moncrieff, Marc; Rytina, E.; Igali, Laszlo

doi:10.1038/bjc.2016.106

Cited by 19 publications

(14 citation statements)

References 17 publications

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“…Immunohistochemical detection of BRAF V600E by VE1 antibody could be a fast and costeffective approach. [43][44][45][46] However, at present, there are important limitations due to a lack of VE1 immunostaining standardization and information concerning the relationship between BRAF gene quantitative allelic variations and its protein expression level.…”

Section: Discussionmentioning

confidence: 99%

High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients

et al. 2021

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Background: BRAF mutant melanoma patients are commonly treated with anti-BRAF therapeutic strategies. However, many factors, including the percentage of BRAF-mutated cells, may contribute to the great variability in patient outcomes.Patients and methods: The BRAF variant allele frequency (VAF; defined as the percentage of mutated alleles) of primary and secondary melanoma lesions, obtained from 327 patients with different disease stages, was assessed by pyrosequencing. The BRAF mutation rate and VAF were then correlated with melanoma pathological features and patients' clinical characteristics. KaplaneMeier curves were used to study the correlations between BRAF VAF, overall survival (OS), and progression-free survival (PFS) in a subset of 62 patients treated by anti-BRAF/anti-MEK therapy after metastatic progression. Results: A highly heterogeneous BRAF VAF was identified (3%-90%). Besides being correlated with age, a higher BRAF VAF level was related to moderate lymphocytic infiltration (P ¼ 0.017), to melanoma thickness according to Clark levels, (level V versus III, P ¼ 0.004; level V versus IV, P ¼ 0.04), to lymph node metastases rather than cutaneous (P ¼ 0.04) or visceral (P ¼ 0.03) secondary lesions. In particular, a BRAF VAF >25% was significantly associated with a favorable outcome in patients treated with the combination of anti-BRAF/anti-MEK drug (OS P ¼ 0.04; PFS P ¼ 0.019), retaining a significant value as an independent factor for the OS and the PFS in the multivariate analysis (P ¼ 0.014 and P ¼ 0.003, respectively). Conclusion: These results definitively support the role of the BRAF VAF as a potential prognostic and predictive biomarker in melanoma patients in the context of BRAF inhibition.

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Section: Discussionmentioning

confidence: 99%

High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients

et al. 2021

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“…In metastatic melanoma, although genomic assays are the gold standard, the sensitivity and specificity of BRAF VE1 for determining the presence of a BRAF V600 mutation are >94%, and the use of BRAF IHC followed by genomic assays in patients with negative IHC results for BRAF is recommended in order to increase the patient number with detected BRAF mutations compared with that using either assay alone ( 19 ). To understand the reliability of BRAF VE1 IHC analyses, studies with a greater number of cases should be performed.…”

Section: Discussionmentioning

confidence: 99%

“…Anti-BRAF V600E (clone VE1), a mouse monoclonal primary antibody [anti-BRAF V600E (VE1)] is used in the identification of the mutant BRAF V600E protein. BRAF VE1 has been successfully validated in malignant melanoma, colorectal carcinoma, papillary thyroid carcinoma, lung cancer and PXA ( 13 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

BRAF V600E mutation and BRAF VE1 immunoexpression profiles in different types of glioblastoma

et al. 2018

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Abnormalities in proto-oncogene B-Raf (BRAF) are typical in several subgroups of gliomas, including pilocytic astrocytomas, optic nerve gliomas, pleomorphic xanthoastrocytomas (PXA), anaplastic PXAs and gangliogliomas. However, they are rarely reported in adult gliomas. BRAF alterations are frequent in a distinct variant of glioblastomas (GBMs) known as epithelioid GBMs (E-GBMs). There are limited studies on whether immunohistochemistry (IHC) can be used to determine the presence of BRAF VE1 mutations in these tumors. The aim of the current study was to examine BRAF V600E mutations in 20 GBMs, including GBMs with epithelioid features, giant cell GBMs and conventional GBMs. V600 mutations were detected using the Cobas 4800 BRAF V600 Mutation Test, and IHC analysis was also performed. Of the 6 cases of GBM with epithelioid features, 1 exhibited a BRAF V600E mutation, while the other cases did not. IHC staining was positive in 3 out of the 8 conventional GBMs. Vemurafenib is a targeted therapy that has mainly been used for the treatment of melanoma patients for several years, and as a possible alternative treatment for cases of GBM harboring BRAF mutations, its existence may make testing for BRAF status important.

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“…The sample was concluded as having a "BRAFV600E/D mutation" (screenshot of the Idylla™ automated report). with molecular methods in melanoma samples (11)(12)(13)(14)(15)(21)(22)(23). Because IHC is easy to automate and is a widely distributed technique in comparison with molecular methods, it could be an interesting ancillary tool to provide a fast mutation status analysing FFPE melanoma samples in pathology laboratories.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a Rapid, Fully Automated Platform for Detection of BRAF and NRAS Mutations in Melanoma

Barel¹,

Guibourg²,

Lambros³

et al. 2018

Acta Derm Venerol

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BRAF and NRAS genetic analyses are time-consuming and can delay treatment choices in patients with metastatic melanomas presenting with acute deterioration. We compared the rapid, real-time, fully automated molecular diagnosis platform Idylla™ with next-generation sequencing (NGS) and immunohistochemistry for detection of BRAF and NRAS mutations in 36 patients with metastatic melanomas. The Idylla™ NRAS-BRAF-EGFRS492R mutation assay (110 min per sample) detected BRAF and NRAS mutations in 15 and 17 samples, respectively. One NRAS mutation was different between NGS and Idylla™ (NRASG13C vs. NRASG12A/D). Four samples were BRAF and NRAS wild-type. The global concordance between NGS and Idylla™ assays was 97.2% (35/36 cases). Immunohistochemistry was positive only in 9/9 BRAFV600E- and 6/6 NRASQ61R-mutated samples with VE1 and SP174 antibodies, respectively. The Idylla™ platform is a valuable rapid molecular diagnosis tool to reduce the delay in BRAF and NRAS analyses-related treatment choices for patients with metastatic melanoma presenting with acute deterioration.

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A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma

Cited by 19 publications

References 17 publications

High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients

High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients

BRAF V600E mutation and BRAF VE1 immunoexpression profiles in different types of glioblastoma

Evaluation of a Rapid, Fully Automated Platform for Detection of BRAF and NRAS Mutations in Melanoma

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