Stains & CD markers
Transducin-like enhancer of split 1 (TLE1)

Editor-in-Chief: Debra L. Zynger, M.D.
Anna Dusenbery, M.D.
Mark R. Wick, M.D.

Topic Completed: 1 March 2018

Minor changes: 17 June 2021

Copyright: 2018-2022,, Inc.

PubMed Search: "Transducin-like enhancer of split 1" OR TLE1[TI]

Anna Dusenbery, M.D.
Mark R. Wick, M.D.
Page views in 2021: 8,592
Page views in 2022 to date: 562
Cite this page: Dusenbery A. Transducin-like enhancer of split 1 (TLE1). website. Accessed January 28th, 2022.
Definition / general
Clinical relevance
  • Synovial sarcoma is currently the most common target for diagnostic TLE1 immunostaining
  • Repression by TLE1 depends on histone deacetylase (HDAC) activity
    • Research involving HDAC inhibitors and synovial sarcoma supports the premise that, through this connection, TLE1 may be involved in the pathophysiology of synovial sarcoma
    • May thus be a therapeutically useful target in the future (Eur J Cancer 2010;46:1170)
Uses in diagnostic anatomic pathology
  • Reasonably sensitive and specific for synovial sarcoma, including its monophasic, biphasic and poorly differentiated forms
  • TLE1 immunohistochemistry is less costly and has a faster turnaround time than SS18 break apart studies by fluorescence in situ hybridization (FISH) in the diagnosis of synovial sarcoma (Appl Immunohistochem Mol Morphol 2013;21:408)
  • TLE1 immunostains can be useful in identifying a specific subpopulation of tumor cells for t(X;18) FISH analysis or those showing cryptic X;18 rearrangement (Am J Surg Pathol 2009;33:1743)
Laboratory considerations
Microscopic (histologic) images

Contributed by Mark R. Wick, M.D.

Monophasic synovial sarcoma H&E

Monophasic synovial sarcoma TLE1

Biphasic synovial sarcoma H&E

Biphasic synovial sarcoma TLE1

Contributed by Debra Zynger, M.D.

Monophasic synovial sarcoma H&E

Monophasic synovial sarcoma TLE1 positive

Malignant peripheral nerve sheath tumor H&E

Malignant peripheral nerve sheath tumor TLE1 negative

Positive staining - normal tissues
Positive staining - pathologic conditions
Positive staining - pathologic conditions
  • Intense, diffuse nuclear staining with only rare background or cytoplasmic labeling is expected in synovial sarcoma (SS), including all of its histologic subtypes (Am J Surg Pathol 2009;33:1743, Am J Clin Pathol 2011;135:839)
  • TLE1 was previously regarded as both highly sensitive and specific for SS but further testing has shown instances of reactivity in other diagnostic entities as well
    • Those lesions include some that are in the morphologic differential diagnosis of SS and others that are not
    • Most TLE1+ tumors besides SS show only focal and weak to moderate labeling as opposed to strong, diffuse and nuclear reactivity in SS (Arch Pathol Lab Med 2015;139:106)
  • Among the most commonly mentioned non-SS lesions that may occasionally stain for TLE1 are:
    • Peripheral nerve sheath tumors (including neurofibroma, schwannoma and malignant peripheral nerve sheath tumor), solitary fibrous tumor / hemangiopericytoma, rhabdomyosarcoma, leiomyosarcoma, Ewing sarcoma / peripheral neuroectodermal tumor, high grade chondrosarcoma and clear cell sarcoma
    • Rarely, "carcinosarcoma" (sarcomatoid carcinoma), atypical fibroxanthoma, SETTLE (spindle epithelial tumor with thymus-like differentiation), GIST (gastrointestinal stromal tumor), undifferentiated pleomorphic sarcoma, mesothelioma and endometrial stromal sarcoma may manifest limited TLE1 immunoreactivity (Mod Pathol 2009;22:872, Am J Surg Pathol 2007;31:240, Am J Surg Pathol 2009;33:1179, Virchows Arch 2010;457:577)
  • TLE1 overexpression has been seen to varying degrees in invasive adenocarcinomas of the breast (J Breast Cancer 2017;20:45), stomach (J Gastric Cancer 2016;16:21) and lung (Cancer Res 2006;66:1294)
  • TLE1 immunoreactivity has been demonstrated in sarcomas with BCOR-CCNB3 gene fusion: 6/11 cases of undifferentiated sarcoma (Am J Surg Pathol 2017;41:1713), and 2/2 cases of primary renal sarcoma (Am J Surg Pathol 2017;41:1702)‚Äč
Negative staining
Board review style question #1
Which of the following pathways is inhibited by TLE1?

  1. Hedgehog signaling pathway
  2. JAK-STAT signaling pathway
  3. Mitogen activated protein kinase (MAPK) signaling pathway
  4. TGF beta signaling pathway
  5. Wnt / beta catenin signaling pathway
Board review style answer #1
E. Wnt / beta catenin signaling pathway

Comment Here

Reference: Transducin-like enhancer of split 1 (TLE1)
Board review style question #2
Which of the following shows diffuse nuclear staining for TLE1?

  1. Biphasic synovial sarcoma
  2. Monophasic synovial sarcoma
  3. Poorly differentiated synovial sarcoma
  4. All of the above
  5. None of the above
Board review style answer #2
Board review style question #3
Which of the following translocations is associated with synovial sarcoma?

  1. t(2;5)
  2. t(11;22)
  3. t(14;18)
  4. t(17;22)
  5. t(X;18)
Board review style answer #3
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