Stains
SMARCA4/BRG1


Topic Completed: 5 March 2019

Revised: 8 December 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: SMARCA4/BRG1

Susan M. Armstrong, M.D., Ph.D.
Brendan C. Dickson, M.D., M.Sc.
Page views in 2019 to date: 1,323
Cite this page: Armstrong SM, Dickson BC. SMARCA4/BRG1 . PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsSMARCA4BRG1.html. Accessed December 13th, 2019.
Definition / general
  • SMARCA4 (SWI / SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) encodes a protein involved in chromatin remodeling, which is important for regulating the binding of transcription factors to DNA (also known as BRG1 and hSNF2β, amongst others; NCBI Gene ID: 6597)
  • As an evolutionarily conserved regulator of many transcription factors, it is important in mammalian tissue development and differentiation (Trends Genet 2007;23:403, Mol Cell Biol 2011;31:2618)
Essential features
Pathophysiology
Clinical features
  • Heterozygous germline SMARCA4 mutations are associated with an autosomal dominant condition known as rhabdoid tumor predisposition syndrome-2 (OMIM #613325)
  • A subset of patients with Coffin-Siris syndrome, specifically CSS4, a congenital malformation syndrome, bear a heterozygous germline SMARCA4 mutation (OMIM #614609)
Interpretation
  • SMARCA4 has a nuclear pattern of immunohistochemical expression (Nature 1993;366:170); SMARCA4 deficient neoplasms have complete loss of staining amongst tumor cells with retained expression by nonneoplastic tissues (e.g., blood vessels, lymphocytes)
  • There is no established cutoff for determining high versus low expression; staining of the surrounding normal tissue has been used as a median value relative to which SMARCA4 expression may be considered increased or decreased (Int J Oncol 2013;42:403)
Uses by pathologists
Prognostic factors
  • Concomitant loss of SMARCA4 and BRM in non small cell lung cancer is associated with worse prognosis (Cancer Res 2003;63:560)
  • Loss of expression of SMARCA4 is associated with improved prognosis in clear cell renal cell carcinoma (Oncotarget 2017;8:37423)
  • Increased SMARCA4 expression is associated with worse prognosis in patients with breast invasive ductal carcinoma (Anticancer Res 2016;36:4873), hepatocellular carcinoma and clear cell renal cell carcinoma (Sci Rep 2018;8:2043)
Microscopic (histologic) images

Contributed by Rose Chami, M.D. and Catherine Chung, M.D.

Ovarian small cell carcinoma, hypercalcemic type

Positive staining - normal
  • Most normal tissues contain intact nuclear SMARCA4 expression
Negative staining - normal
  • Not applicable
Positive staining - disease
Negative staining - disease
Molecular / cytogenetics description
  • In small cell carcinoma of the ovary, whole exome sequencing demonstrated
  • In SMARCA4 deficient thoracic sarcoma, mRNA sequencing showed the presence of SMARCA4 gene mutations (nonsense, frameshift, missense and splice site) (Nat Genet 2015;47:1200)
Board review question #1
    Which of the following is associated with loss of SMARCA4 expression?

  1. Colorectal adenocarcinoma
  2. Melanoma
  3. Small cell carcinoma of the lung
  4. Small cell carcinoma of the ovary, hypercalcemic type
Board review answer #1
D. Small cell carcinoma of the ovary, hypercalcemic type

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