Stains & CD markers

Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.

Topic Completed: 1 July 2018

Minor changes: 17 September 2021

Copyright: 2018-2021,, Inc.

PubMed Search: TFE3 stain

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Cite this page: Alikhan M. TFE3. website. Accessed September 22nd, 2021.
Definition / general
  • TFE3 gene is located on Xp11.2
  • Encodes a transcription factor that binds to the immunoglobulin heavy chain enhancer 3
  • Member of the same family of transcription factors as microphthalmia transcription factor (MiTF), TFEB and TFEC
  • As a homodimer or heterodimer (e.g. with TFEB), promotes the expression of a wide variety of genes involved in cell growth and proliferation
  • Overactivation (i.e. by translocations) can result in oncogenic activation
  • About a dozen translocation partners identified, with PRCC and ASPSCR1 being the most common in renal cell carcinomas
Essential features
Uses by pathologists
  • Differentiate MiT family translocation associated renal cell carcinoma from other types of renal cell carcinoma, particularly those with clear cell morphology and papillary architecture
  • Aids in the diagnosis of alveolar soft part sarcoma and predicts the presence of the translocation by FISH
  • Subset of epithelioid hemangioendotheliomas, PEComas and solid pseudopapillary neoplasms of the pancreas may also be positive for TFE3
Prognostic factors
  • Children and young adults with MiT family translocation associated renal cell carcinoma generally show a good prognosis
  • Older adults with renal cell carcinoma harboring TFE3 rearrangement by FISH tend to show a worse prognosis (Am J Surg Pathol 2012;36:663)
  • Diffuse nuclear expression in the neoplastic cells
Microscopic (histologic) images

Contributed by Mir Alikhan, M.D.

Xp11 translocation renal cell carcinoma (H&E and TFE3 immunostain)

Melanotic Xp11 renal cell carcinoma (H&E and TFE3 immunostain)

Positive staining - normal
  • TFE3 protein is expressed in a wide variety of tissues, particularly in the genitourinary tract but is often weak (J Clin Pathol 2006;59:1127)
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:


ASPL-TFE3 sequence

ASPL-TFE3 FISH, RT-PCR and sequence

Board review style question #1
Translocations involving the TFE3 gene can be found in which of the following neoplasms?

  1. Angiosarcoma
  2. Clear cell papillary renal cell carcinoma
  3. Clear cell sarcoma
  4. Melanotic perivascular endothelial cell tumor
  5. Solid pseudopapillary pancreatic neoplasm
Board review style answer #1
D. TFE3 fusions are most closely associated with Xp11 translocation renal cell carcinoma, alveolar soft part sarcoma, melanotic Xp11 RCC, some PEComas and others. Although increased TFE3 expression is seen in some solid pseudopapillary pancreatic neoplasms, these have been negative for the gene fusion.

Reference: Stains - TFE3

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Board review style question #2
Which of the following is a common, effective method for detection of the TFE3 gene fusion?

  1. Break apart FISH probe
  2. Conventional karyotype analysis
  3. Dual color, dual fusion FISH probe
  4. Immunohistochemistry
  5. RNA sequencing
Board review style answer #2
A. Due to the multiple translocation partners seen in TFE3 associated neoplasms, a break apart FISH probe is recommended over a dual color, dual fusion FISH probe. Some fusions are cryptic and cannot be detected by conventional karyotype analysis. Immunohistochemistry would detect the overexpression of TFE3 but cannot confirm whether the overexpression is due to the fusion event or other, possibly epigenetic, factors leading to TFE3 overexpression. RNA sequencing can detect the multiple fusion partners but is not commonly utilized at this time.

Reference: Stains - TFE3

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