Stains & CD markers
TFE3

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Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.

Last author update: 23 May 2022
Last staff update: 23 May 2022

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PubMed Search: TFE3 stain pathology

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Cite this page: Alikhan M. TFE3. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainstfe3.html. Accessed August 11th, 2022.
Definition / general
  • TFE3 gene, located on Xp11.2, is translocated with > 20 of partner genes in a variety of tumor types, most commonly in MiT family translocation renal cell carcinoma (RCC)
  • Translocation often leads to upregulation of TFE3 and subsequent cell proliferation and oncogenesis
  • TFE3 gene translocation results in aberrant overexpression of the fusion oncoprotein which can be detected by a C terminus binding site TFE3 antibody (Adv Anat Pathol 2022;29:131)
Essential features
Pathophysiology
  • TFE3 gene encodes a transcription factor
  • As a homodimer or heterodimer with MiT related proteins (such as TFEB), it promotes the expression of a wide variety of genes involved in cell growth and proliferation
  • These proteins also bind DNA transcription enhancing sites to regulate cellular catabolism and nutrient dependent lysosomal response (Nat Commun 2019;10:3623)
  • Due to their association with MiT, they may express melanocytic markers and downregulate expression of cytokeratins
Clinical features
  • MiT family translocation renal cell carcinoma, like many other MiT related tumors, is more commonly seen in children and young adults
Interpretation
  • Diffuse strong nuclear expression in the neoplastic cells
Uses by pathologists
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)
Microscopic (histologic) images

Contributed by Mir Alikhan, M.D.

Xp11 translocation renal cell carcinoma

Melanotic Xp11 renal cell carcinoma

Positive staining - normal
Positive staining - disease
  • MiT family translocation associated renal cell carcinoma
  • Granular cell tumor (Hum Pathol 2014;45:1039)
  • Alveolar soft part sarcoma
  • Subset of epithelioid hemangioendotheliomas
  • Subset of perivascular endothelial cell tumors (PEComas)
  • Some solid pseudopapillary pancreatic neoplasms
  • Subset of ovarian sclerosing stromal tumors
Negative staining
  • Clear cell, papillary, clear cell papillary, FH deficient and chromophobe type renal cell carcinoma
  • Clear cell sarcoma
  • Reference: Am J Surg Pathol 2003;27:750
Molecular / cytogenetics description
  • TFE3 break apart probes in FISH analysis are most effective at detection of the fusion due to multiple partners of the gene
  • Most common partner genes in MiT family translocation associated renal cell carcinoma are PRCC and ASPSCR1 (ASPL) (Am J Surg Pathol 2016;40:723)
  • SFPQ and NONO are also common partners in certain cases of PEComas (Am J Surg Pathol 2015;39:1181, Histopathology 2016;69:450, Am J Surg Pathol 2017;41:717)
  • Fusion most commonly seen in alveolar soft part sarcoma is ASPSCR1 (ASPL) (Oncogene 2001;20:48)
  • Epithelioid hemangioendotheliomas often show WWTR1-CAMTA1 fusions but a subset can also show concomitant YAP1-TFE3 (Oncotarget 2016;7:7480)
  • Reverse transcriptase polymerase chain reaction (PCR) studies can be performed for a more sensitive detection of the fusion product
    • More recently, next generation sequencing using mapping based data mining of sequencing reads can also detect fusions (Am J Surg Pathol 2017;41:1576)
    • Some studies have shown RNA sequencing to be an effective method for novel gene fusion detection (Mod Pathol 2018;31:1346)
  • While granular cell tumor expresses TFE3 by immunohistochemistry, it does not show TFE3 gene rearrangements by FISH (Hum Pathol 2015;46:1242)
Molecular / cytogenetics images

Images hosted on other servers:

TFE3 FISH

ASPL-TFE3 sequence

ASPL-TFE3 FISH, RT-PCR and sequence

Sample pathology report
  • Right kidney, total nephrectomy:
    • MiT family translocation renal cell carcinoma, TFE3 positive
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. Melanotic perivascular endothelial cell tumor. TFE3 fusions are most closely associated with Xp11 translocation renal cell carcinoma, alveolar soft part sarcoma, melanotic Xp11 renal cell carcinoma, some PEComas and others. Although increased TFE3 expression is seen in some solid pseudopapillary pancreatic neoplasms, these have been negative for the gene fusion.

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Reference: TFE3
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. Break apart FISH probe. 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. While RNA sequencing can detect the multiple fusion partners, it is not commonly utilized at this time.

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Reference: TFE3
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