Pathology Outlines

Stains
BRAF

Author: Nat Pernick, M.D.

Topic Completed: 1 January 2012

Minor changes: 2 June 2020

Copyright: 2003-2019, PathologyOutlines.com, Inc.

PubMed Search: BRAF[title]

See also BRAF-melanoma

Page views in 2019: 3,649

Page views in 2020 to date: 2,297

Table of Contents

Cite this page: Pernick N. BRAF. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsbraf.html. Accessed July 10th, 2020.

Definition / general

Serine / threonine specific protein kinase, part of the RAS / MAPK pathway regulating the growth, maturation, proliferation, survival and apoptosis of cells
Abbreviation for v-raf murine sarcoma viral oncogene homolog B1
Gene commonly mutated in papillary thyroid carcinoma and melanoma
V600E mutation (valine at residue 600 replaced by glutamic acid) renders BRAF constitutively active and increases its kinase activity (Nature 2002;417:949)
IHC with VE1 antibody is highly sensitive and specific to detect BRAF V600E mutation (Virchows Arch 2015;467:155)

Diagrams / tables

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MAPK signaling pathway

Clinical features

The drug Vemurafenib / Zelboraf®, used to treat melanoma, interrupts the BRAF / MEK / ERK pathway, only when BRAF has the V600E mutation (valine replaced by glutamic acid)

Uses by pathologists

Colorectal carcinoma: differentiate Lynch syndrome (BRAF negative) from sporadic MSI tumors (BRAF mutation in 40% - 50%); mutation analysis for anti EGFR treatment (Arch Pathol Lab Med 2011;135:578), prognostic value (Arch Pathol Lab Med 2010;134:1225)
Melanoma: mutation analysis for treatment (Vemurafenib, N Engl J Med 2011;364:2507, J Skin Cancer 2011;2011:423239); may provide prognostic information (Arch Pathol Lab Med 2011;135:860)
Thyroid: mutation analysis for thyroid FNA to detect papillary carcinoma (Endocr J 2007;54:399, Hum Pathol 2012;43:89), prognostic value (Arch Pathol Lab Med 2011;135:569)

Microscopic (histologic) images

Images hosted on PathOut server:

Courtesy of Andrey Bychkov, M.D., Ph.D.

V600E mutant protein is diffusely expresed in tumor / cancer, but not normal tissue

Diffuse cytoplasmic staining

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Prevalence of BRAF mutations
in different histologic variants
of thyroid papillary carcinoma

Negative stains

Ewing sarcoma (Hum Pathol 2011;43:1077)

Molecular / cytogenetics description

Anus: anorectal melanoma (5%, Hum Pathol 2011;43:801)
CNS: pilocytic astrocytomas (most, Arch Pathol Lab Med 2011;135:558), pleomorphic xanthoastrocytoma (60%, PLoS One 2011;6:e17948)
Colon: serrated adenoma (Cancer Res 2003;63:4878), serrated fibroblastic polyps / intramucosal perineuriomas (63%, Am J Surg Pathol 2010;34:1663), colorectal carcinoma (V600E mutation occurs in 40% - 50% of sporadic MSI colorectal cancers, Arch Pathol Lab Med 2011;135:1269)
Esophagus: 1 of 10 melanomas (Mod Pathol 2011;24:495)
GIST (13% of wild type, Am J Clin Pathol 2010;133:141)
Leukemia/lymphoma: hairy cell leukemia (60-100%, Haematologica 2011;97:780, N Engl J Med 2011;364:2305) versus none / rare in other B cell leukemia / lymphomas
Lung: micropapillary adenocarcinoma (20%, Am J Clin Pathol 2009;131:694)
Lymph nodes: benign nevi (Am J Surg Pathol 2009;33:568)
Ovary: malignant struma ovarii (Am J Surg Pathol 2007;31:1337)
Skin: congenital pattern nevi (71%, J Invest Dermatol 2007;127:179), nevi (81%, Am J Dermatopathol 2007;29:534); Langerhans cell histiocytosis (57%, Blood 2010;116:1919), melanoma (50% have V600E mutation; these tumors are usually not associated with sun damage)
Thyroid: Spitz nevi (some, Mod Pathol 2006;19:1324), anaplastic carcinoma (50%); papillary thyroid carcinoma (36-69%, Arch Pathol Lab Med 2011;135:569); less common in follicular variant than classic (31% versus 58%, Hum Pathol 2011;42:500), rare in diffuse sclerosing variant (Mod Pathol 2007;20:779); not found in Hashimoto's thyroiditis (Am J Clin Pathol 2009;132:906)

Molecular / cytogenetics images

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BRAF melting curves