Please confirm you are human (Sign Up for free to never see this)
← Back to Search
Assessment Of BRAF V600E Mutation Status By Immunohistochemistry With A Mutation-specific Monoclonal Antibody
D. Capper, M. Preusser, A. Habel, F. Sahm, U. Ackermann, Genevieve Schindler, S. Pusch, G. Mechtersheimer, H. Zentgraf, A. Deimling
Published 2011 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Activating mutations of the serine threonine kinase v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) are frequent in benign and malignant human tumors and are emerging as an important biomarker. Over 95% of BRAF mutations are of the V600E type and specific small molecular inhibitors are currently under pre-clinical or clinical investigation. BRAF mutation status is determined by DNA-based methods, most commonly by sequencing. Here we describe the development of a monoclonal BRAF V600E mutation-specific antibody that can differentiate BRAF V600E and wild type protein in routinely processed formalin-fixed and paraffin-embedded tissue. A total of 47 intracerebral melanoma metastases and 21 primary papillary thyroid carcinomas were evaluated by direct sequencing of BRAF and by immunohistochemistry using the BRAF V600E mutation-specific antibody clone VE1. Correlation of VE1 immunohistochemistry and BRAF sequencing revealed a perfect match for both papillary thyroid carcinomas and melanoma metastases. The staining intensity in BRAF V600E mutated tumor samples ranged from weak to strong. The generally homogenous VE1 staining patterns argue against a clonal heterogeneity of the tumors investigated. Caution is essential when only poorly preserved tissue is available for VE1 immunohistochemical analysis or when tissues with only little total BRAF protein are analyzed. Immunohistochemistry using antibody VE1 may substantially facilitate molecular analysis of BRAF V600E status for diagnostic, prognostic, and predictive purposes.
This paper references
High frequency of BRAF mutations in nevi
P. Pollock (2003)
Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia.
S. Yuen (2002)
Application of Mutant IDH1 Antibody to Differentiate Diffuse Glioma From Nonneoplastic Central Nervous System Lesions and Therapy-induced Changes
D. Capper (2010)
Expression and activation of B-Raf kinase isoforms in human and murine leukemia cell lines.
A. Eychène (1995)
Feasibility of archival non‐buffered formalin‐fixed and paraffin‐embedded tissues for PCR amplification: An analysis of resected gastric carcinoma
T. Inoue (1996)
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
R. Nazarian (2010)
Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors.
R. Kefford (2010)
Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma
G. Schindler (2011)
Inhibition of mutated, activated BRAF in metastatic melanoma.
K. Flaherty (2010)
BRAF mutation in papillary thyroid carcinoma.
Yoram Cohen (2003)
Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression
J. Lin (2011)
Aberrant BRAF splicing as an alternative mechanism for oncogenic B‐Raf activation in thyroid carcinoma
E. Baitei (2009)
IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours
M. F. Amary (2011)
Continuous cultures of fused cells secreting antibody of predefined specificity
G. Köhler (1975)
Monoclonal antibody specific for IDH1 R132H mutation
D. Capper (2009)
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.
W. De Roock (2010)
Recurrent BRAF mutations in Langerhans cell histiocytosis.
G. Badalian-Very (2010)
Detection of KRAS and BRAF mutations in colorectal carcinoma roles for high-sensitivity locked nucleic acid-PCR sequencing and broad-spectrum mass spectrometry genotyping.
M. Arcila (2011)
The Mouse B-raf Gene Encodes Multiple Protein Isoforms with Tissue-specific Expression (*)
J. Barnier (1995)
Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing.
M. Andrulis (2010)
Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site
A. Platz (2008)
Molecular diagnostics of thyroid tumors.
Y. Nikiforov (2011)
High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.
E. Kimura (2003)
Prognostic stratification of gliomatosis cerebri by IDH1R132H and INA expression
V. Desestret (2011)
Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer.
F. Di Nicolantonio (2008)
Characterization of R132H Mutation‐specific IDH1 Antibody Binding in Brain Tumors
D. Capper (2010)
Suppression of oncogenic NRAS by RNA interference induces apoptosis of human melanoma cells
M. Eskandarpour (2005)
Targeting BRAF for patients with melanoma
H. Arkenau (2011)
Metastatic colorectal cancer KRAS genotyping in routine practice: results and pitfalls
A. Lamy (2011)
Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma.
G. Singer (2003)
High frequency of BRAFV600E mutation in acquired nevi and small congenital nevi, but low frequency of mutation in medium-sized congenital nevi.
Nami Ichii-Nakato (2006)
NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing
Esther Edlundh-Rose (2006)
Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF
P. Wan (2004)
BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas.
T. Chan (2003)
This paper is referenced by
BRAF and MAP2K1 mutations in Langerhans cell histiocytosis: a study of 50 cases.
K. Alayed (2016)
How molecular testing can help (and hurt) in the workup of gliomas.
K. Clark (2013)
Enlargement of papillary glioneuronal tumor in an adult after a follow-up period of 10 years: a case report
Yuya Fujita (2018)
Development of ultra-short PCR assay to reveal BRAF V600 mutation status in Thai colorectal cancer tissues
Nunthawut Chat-Uthai (2018)
Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers
P. Sadlecki (2017)
Biopanel identifies expression status of targetable proteins in sinonasal melanoma.
Lisa Grünmüller (2016)
KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas
A. Becker (2015)
Molecular Diagnostics of Gliomas Using Next Generation Sequencing of a Glioma‐Tailored Gene Panel
A. Zacher (2017)
Diencephalic pediatric low-grade glioma harboring the BRAF V600E mutation presenting with various morphologies in sequential biopsy specimens
Yukitomo Ishi (2017)
Extent of Resection, MGMT Promoter Methylation Status and Tumor Location Independently Predict Progression-Free Survival in Adult Sporadic Pilocytic Astrocytoma
C. Jungk (2019)
Histological features of BRAF V600E‐mutant anaplastic thyroid carcinoma
T. Chen (2020)
Immunohistochemistry is highly sensitive and specific for detection of BRAF V600E mutation in pleomorphic xanthoastrocytoma
C. M. Ida (2013)
Analysis of 24 cases of epithelioid glioblastoma: Experience from a tertiary centre of North India.
Debajyoti Chatterjee (2020)
Deficient mismatch repair: Read all about it (Review)
S. Richman (2015)
Development of Protein-Catalyzed Capture (PCC) Agents with Application to the Specific Targeting of the E17K Point Mutation of Akt1
Kaycie M. Deyle (2014)
Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas
P. Brastianos (2014)
Integrating molecular biomarkers into current clinical management in melanoma.
R. Kudchadkar (2014)
Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
C. Gow (2019)
Bone marrow biopsies of patients with hematopoietic and lymphoid disorders - epidemiology, chromosomal aberrations and molecular pathology.
Sophie Hehne (2012)
Response in a child with a BRAF V600E mutated desmoplastic infantile astrocytoma upon retreatment with vemurafenib
C. van Tilburg (2018)
Regression of BRAFV600E mutant adult glioblastoma after primary combined BRAF-MEK inhibitor targeted therapy: a report of two cases
Peter Y M Woo (2019)
Langerhans Cell Histiocytosis, Non-Langerhans histiocytosis and concurrent Papillary Thyroid Carcinoma with BRAF V600E mutations: A case report and literature review
Laura Wake (2019)
BRAF as a therapeutic target: a patent review (2006 – 2012)
A. Zambon (2013)
Immunohistochemical Analysis of BRAFV600E Expression of Primary and Metastatic Melanoma and Comparison With Mutation Status and Melanocyte Differentiation Antigens of Metastatic Lesions
K. Busam (2013)
VE1 immunohistochemical detection of the BRAF V600E mutation in thyroid carcinoma: a review of its usefulness and limitations
Jong-In Na (2015)
Inhibition of the mitochondrial Hsp90 chaperone network: a novel, efficient treatment strategy for cancer?
M. Siegelin (2013)
Intérêt de l’immunohistochimie à visée théranostique dans les carcinomes bronchiques non à petites cellules : applications et limites actuelles
Marius Ilie (2015)
L’immunohistochimie (clone VE1) est une méthode économique, spécifique et sensible pour détecter la présence d’une mutation BRAFV600E dans le mélanome
Michel Étienne (2016)
Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases
D. Capper (2011)
BRAFV600E Immunohistochemistry Facilitates Universal Screening of Colorectal Cancers for Lynch Syndrome
C. Toon (2013)
Tumour‐infiltrating lymphocytes and expression of programmed death ligand 1 (PD‐L1) in melanoma brain metastases
A. Berghoff (2015)
Initial diagnosis of chronic myelogenous leukemia based on quantification of M-BCR status using droplet digital PCR
H. L. Lund (2015)See more