Stains & CD markers
INI1 / SMARCB1
Copyright: 2002-2022, PathologyOutlines.com, Inc.
PubMed Search: INI1 / SMARCB1
INI1 / SMARCB1
Editorial Board Member: Meaghan Morris, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Last author update: 1 June 2022
Last staff update: 1 June 2022
Copyright: 2002-2022, PathologyOutlines.com, Inc.
PubMed Search: INI1 / SMARCB1
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Molecular / cytogenetics description | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Kommoss FKF, Schürch CM. INI1 / SMARCB1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsini1.html. Accessed July 3rd, 2022.
Definition / general
- SMARCB1 (switch / sucrose non fermentable [SWI / SNF] related, matrix associated, actin dependent regulator of chromatin subfamily B member 1) is located on chromosome 22q11.2 and encodes a core subunit of the adenosine triphosphate (ATP) dependent SWI / SNF chromatin remodeling complex, which is actively involved in the regulation of gene expression
Essential features
- SMARCB1 is a core subunit of the SWI / SNF chromatin remodeling complex
- SMARCB1 is considered a bona fide tumor suppressor
- Germline SMARCB1 mutations are associated with rhabdoid tumor predisposition syndrome 1 and familial schwannomatosis
- Loss of SMARCB1 expression is identified in a variety of rhabdoid and nonrhabdoid neoplasms of the CNS, soft tissue and parenchymal / visceral organs
Terminology
- SMARCB1 (SWI / SNF related, matrix associated, actin dependent regulator of chromatin subfamily B member 1), INI1 (integrase interactor 1), BAF47, hSNF5
Pathophysiology
- Core subunit of the ATP dependent SWI / SNF chromatin remodeling complex involved in transcriptional activation and repression through chromatin remodeling
- Bona fide tumor suppressor interacting with other cancer associated pathways (e.g., WNT signaling pathway and hedgehog signaling pathway) (Nat Med 2010;16:1429)
- Initially discovered as a protein that binds HIV integrase (Science 1994;266:2002)
Clinical features
- Germline heterozygous pathogenic variants in SMARCB1 are associated with rhabdoid tumor predisposition syndrome 1 (RTPS1) (OMIM: Rhabdoid Tumor Predisposition Syndrome 1; RTPS1 [Accessed 22 December 2021], Am J Hum Genet 1999;65:1342)
- Germline heterozygous pathogenic variants in SMARCB1 are associated with familial schwannomatosis (J Med Genet 2008;45:332, Neurogenetics 2012;13:141)
Interpretation
- Nuclear stain
Uses by pathologists
- Guides the diagnosis of:
- Malignant rhabdoid tumor (MRT) of kidney and soft tissue and CNS atypical teratoid / rhabdoid tumor (AT / RT): loss of expression (Mod Pathol 2006;19:717)
- Epithelioid sarcoma (ES): loss of expression (Cancer Res 2005;65:4012)
- Renal medullary carcinoma: loss of expression (Histopathology 2012;61:428)
- SMARCB1 deficient sinonasal carcinoma / adenocarcinoma: loss of expression (Am J Surg Pathol 2014;38:1282)
- Poorly differentiated chordoma: loss of expression (Mod Pathol 2018;31:1237)
- Epithelioid benign and malignant peripheral nerve sheath tumors: loss of expression (Am J Surg Pathol 2015;39:673)
- Dedifferentiated / undifferentiated endometrial and ovarian carcinoma: loss of expression (undifferentiated component) (Histopathology 2017;70:359)
- Undifferentiated / rhabdoid carcinoma of the gastrointestinal tract and pancreas: loss of expression (Mod Pathol 2015;28:248)
Prognostic factors
- Currently unknown
Microscopic (histologic) images
Contributed by Andreas von Deimling, M.D. and Thomas Mentzel, M.D.
Atypical teratoid / rhabdoid tumor
Epithelioid sarcoma, proximal type
Positive staining - normal
- SMARCB1 is ubiquitously expressed in the nuclei of all normal human cells
Positive staining - disease
- Most tumors show nuclear expression of SMARCB1
- Synovial sarcoma may show reduced expression of SMARCB1 (Mod Pathol 2010;23:981)
Negative staining
- Malignant rhabdoid tumor (MRT) of kidney and soft tissue and CNS atypical teratoid / rhabdoid tumor (AT / RT): 98% (Mod Pathol 2006;19:717, Am J Surg Pathol 2004;28:1485, Am J Surg Pathol 2004;28:644, Acta Neuropathol 2014;128:453)
- Conventional and proximal type epithelioid sarcoma (ES): 80 - 90% (Mod Pathol 2006;19:717, Cancer Res 2005;65:4012, Am J Surg Pathol 2004;28:1485)
- Renal medullary carcinoma: 100% (Mod Pathol 2006;19:717, Histopathology 2012;61:428)
- SMARCB1 deficient sinonasal carcinoma / adenocarcinoma: 100% (Am J Surg Pathol 2014;38:1274, Am J Surg Pathol 2014;38:1282, Head Neck Pathol 2020;14:465)
- Poorly differentiated chordoma: 100% (Mod Pathol 2018;31:1237)
- Myoepithelial carcinoma of soft tissue: 41% (Am J Surg Pathol 2007;31:1813)
- Epithelioid schwannoma: 42% (Am J Surg Pathol 2017;41:1013)
- Epithelioid malignant peripheral nerve sheath tumor: 67% (Am J Surg Pathol 2015;39:673)
- Extraskeletal myxoid chondrosarcoma: 17% (Am J Surg Pathol 2008;32:1168)
- Undifferentiated carcinoma of the gastrointestinal tract and the pancreas: 5 - 28% (Mod Pathol 2015;28:248, Histopathology 2020;77:46, Am J Surg Pathol 2016;40:544)
- Dedifferentiated / undifferentiated endometrial and ovarian adenocarcinoma (undifferentiated component): 3 - 13% (Histopathology 2017;70:359, Mod Pathol 2016;29:302)
- Desmoplastic myxoid tumor of the pineal region, SMARCB1 mutant: 100% (Acta Neuropathol 2020;139:277)
- Cribriform neuroepithelial tumor (CRINET): 90% (J Neuropathol Exp Neurol 2009;68:1249)
Molecular / cytogenetics description
- Malignant rhabdoid tumors (MRT) of kidney and soft tissue as well as CNS atypical teratoid / rhabdoid tumor (AT / RT): point and frameshift mutations, deletions or translocations involving SMARCB1 and monosomy 22 (Pediatr Blood Cancer 2011;56:7)
- Epithelioid sarcoma: homozygous deletion of SMARCB1 can be demonstrated by FISH in most (90%) cases (Genes Chromosomes Cancer 2014;53:475)
- Medullary renal carcinoma: translocations and heterozygous deletion of SMARCB1 in most cases (Eur Urol 2016;69:1055)
- SMARCB1 deficient sinonasal carcinoma / adenocarcinoma: homozygous deletion of SMARCB1 can be demonstrated by FISH in most (68%) cases; heterozygous deletion or truncating mutation identified in a subset of cases (Hum Pathol 2020;104:105)
- Poorly differentiated chordoma: homozygous deletion of SMARCB1 can be demonstrated by FISH in most (90%) cases (Acta Neuropathol 2016;132:149, Genes Chromosomes Cancer 2018;57:89)
- Myoepithelial carcinoma of soft tissue: homozygous deletion of SMARCB1 can be demonstrated by FISH in a subset of cases (Genes Chromosomes Cancer 2014;53:475)
- Epithelioid benign and malignant peripheral nerve sheath tumors: nonsense, frameshift and splice site mutations as well as deletions in SMARCB1 (Am J Surg Pathol 2019;43:835)
- Dedifferentiated / undifferentiated endometrial and ovarian adenocarcinoma: nonsense and frameshift mutations in SMARCB1 can be identified in a subset of cases (Mod Pathol 2016;29:1586)
Board review style question #1
Which of the following neoplasms is associated with loss of SMARCB1 expression?
- Basal cell carcinoma
- Embryonal rhabdomyosarcoma
- Leiomyosarcoma
- Malignant rhabdoid tumor of the kidney
- Merkel cell carcinoma
Board review style answer #1
Board review style question #2
Which of the following is typically lost in CNS atypical teratoid / rhabdoid tumors (AT / RT)?
- BAP1
- CDKN2A
- NF1
- PTEN
- SMARCB1
Board review style answer #2
