Stains & molecular markers
BRAF
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: BRAF[title]
See also BRAF-melanoma
BRAF
Author: Nat Pernick, M.D.
Topic Completed: 1 January 2012
Minor changes: 25 September 2020
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: BRAF[title]
See also BRAF-melanoma
Table of Contents
Definition / general | Diagrams / tables | Clinical features | Uses by pathologists | Microscopic (histologic) images | Negative stains | Molecular / cytogenetics descriptionCite this page: Pernick N. BRAF. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsbraf.html. Accessed October 20th, 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
Images hosted on other servers:
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
Contributed by Andrey Bychkov, M.D., Ph.D.
V600E mutant protein is diffusely expresed in tumor / cancer, but not normal tissue
Diffuse cytoplasmic staining
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)
