Stains & CD markers
BRAF V600E


Minor changes: 15 July 2021

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PubMed Search: BRAF V600E[TI] free full text[sb] stains

See Also: BRAF-melanoma

Andrew J. Colebatch, M.B.B.S., Ph.D.
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Cite this page: Colebatch A. BRAF V600E. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsbraf.html. Accessed August 2nd, 2021.
Definition / general
  • BRAF is a serine / threonine kinase, part of the MAPK signaling pathway
  • Abbreviation for v-raf murine sarcoma viral oncogene homolog B1
  • BRAF V600E (Val600Glu) is an activating somatic mutation
Essential features
  • BRAF V600E mutations can be reliably detected using immunohistochemistry
  • BRAF V600E status is important therapeutically in melanoma
  • Interpretation can be difficult due to melanin pigment
Terminology
  • BRAF VE1 (antibody)
  • BRAF V599E (older designation of mutation)
Pathophysiology
  • Majority due to thymine to adenine transversion at position 1799 in exon 15 of BRAF
  • Minority are due to an insertion deletion of 2 adenines at positions 1798 and 1799 in exon 15 of BRAF (V600E2)
  • Both mutations result in an identical BRAF V600E protein, which is detected by the antibody
Diagrams / tables

Images hosted on other servers:

MAPK signaling pathway

Interpretation
  • Cytoplasmic stain
  • Melanin pigment and hemosiderin can mimic brown chromogen, making interpretation of heavily pigmented lesions very difficult (if not impossible)
  • Variation in staining can be due to cautery, necrosis, storage time in archive and previous frozen section (Acta Neuropathol 2011;122:11)
Uses by pathologists
Microscopic (histologic) images

Contributed by Andrew Colebatch, M.B.B.S., Ph.D. and Andrey Bychkov, M.D., Ph.D.
BRAF V600E positive nevus BRAF V600E positive nevus BRAF V600E positive nevus

BRAF V600E positive nevus

BRAF V600E positive melanoma

BRAF V600E positive melanoma


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

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

Diffuse cytoplasmic staining

Diffuse cytoplasmic staining

Positive staining - normal
  • Nil
Positive staining - disease
Negative staining
Sample pathology report
  • Soft tissue, perinephric, biopsy:
    • Histiocytic neoplasm with BRAF V600E mutation by immunohistochemistry, consistent with Erdheim-Chester disease in the appropriate clinical context (see comment)
    • Comment: The histologic sections demonstrate adipose tissue with an infiltrate of foamy histiocytes admixed with scattered Touton giant cells. There is extensive fibrosis present. Immunoperoxidase studies were performed on paraffin embedded sections using antibodies directed against the following antigens: CD1a, CD68, CD163, factor XIIIa, IgG, IgG4, langerin, S100 and BRAF V600E. The foamy histiocytes are positive for CD68, CD163 and factor XIIIa and are negative for S100, CD1a and langerin. The lesional histiocytes are positive for BRAF V600E mutation by immunohistochemistry. There is no increase in number of IgG4 positive plasma cells or an abnormal IgG4/IgG ratio.
Board review style question #1

Which of the following statements is true regarding BRAF V600E mutations?

  1. They do not occur in melanoma
  2. They do not occur in papillary craniopharyngioma
  3. They do not occur in adamantinomatous craniopharyngioma
  4. They do not occur in papillary thyroid carcinoma
Board review style answer #1
C. Adamantinomatous craniopharyngiomas do not show BRAF V600E mutations (these tumors show WNT pathway activation with beta catenin mutations).

Comment Here

Reference: BRAF V600E
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