Transducin-like enhancer of split 1 (TLE1)

Stains
Transducin-like enhancer of split 1 (TLE1)

Authors: Anna Dusenbery, M.D., Mark R. Wick, M.D.

Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 1 March 2018

Revised: 8 December 2019

Copyright: 2018, PathologyOutlines.com, Inc.

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

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Table of Contents

Cite this page: Dusenbery A. Transducin-like enhancer of split 1 (TLE1). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainstle1.html. Accessed April 1st, 2020.

Definition / general

TLE1 stands for "transducin-like enhancer of split 1," which is one of 4 TLE genes (Indian J Med Res 2012;136:766)
Located at chromosome 9q21.32 (Appl Immunohistochem Mol Morphol 2013;21:408)
Is a transcriptional corepressor, homologous to the corepressor groucho in Drosophila
- Affects signaling pathways relating to embryogenesis, hematopoiesis and differentiation, specifically lateral inhibition, segmentation, sex determination, eye development and neuronal differentiation (Appl Immunohistochem Mol Morphol 2013;21:408, Arch Pathol Lab Med 2015;139:106)
- Ultimately involved in modulating differentiation through several pathways, including inhibition of the Wnt / beta catenin signaling cascade (Am J Surg Pathol 2007;31:240)
Interacts with many proteins that are involved in cellular proliferation (Virchows Arch 2011:459:615)

Clinical relevance

Synovial sarcoma is currently the most common target for diagnostic TLE1 immunostaining
- Relatively more chemosensitive than other adult soft tissue sarcomas (Indian J Med Res 2012;136:766)
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
- In one study, 22/28 (79%) of monophasic, 18/23 (78%) of biphasic, and 20/22 (91%) of poorly differentiated synovial sarcomas demonstrated nuclear immunoreactivity for TLE1 (Am J Clin Pathol 2011;135:839)
- Exact sensitivity and specificity has been varied in several publications (Arch Pathol Lab Med 2015;139:106)
- Sensitivity ranges from 85 - 100% and specificity ranges from 75 - 96% based on the following two sources, however, there is variation among sources: Mod Pathol 2009;22:872, Am J Surg Pathol 2009;33:1743
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

Monoclonal TLE1 antibody has a better overall immunohistochemistry performance profile than polyclonal TLE1 antibody (Appl Immunohistochem Mol Morphol 2017 Aug 9 [Epub ahead of print])

Microscopic (histologic) images

Images hosted on PathOut server:

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.

H&E

TLE1 positive

Monophasic synovial sarcoma

H&E

TLE1 negative

Malignant peripheral nerve sheath tumor

Positive staining - normal tissues

Basal keratinocytes, adipocytes, perineurial cells, endothelial cells and mesothelial cells (Arch Pathol Lab Med 2015;139:106)

Positive staining - pathologic conditions

Basal keratinocytes, adipocytes, perineurial cells, endothelial cells and mesothelial cells (Arch Pathol Lab Med 2015;139:106)

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)

Negative staining

See the tumor list under positive staining - pathologic conditions above
- Those entities are most often completely nonreactive for TLE1 but may demonstrate occasional positivity

Board review style question #1

Which of the following pathways is inhibited by TLE1?

Hedgehog signaling pathway
JAK-STAT signaling pathway
Mitogen activated protein kinase (MAPK) signaling pathway
TGF beta signaling pathway
Wnt / beta catenin signaling pathway

Board review answer #1

E. Wnt / beta catenin signaling pathway

Board review style question #2

Which of the following shows diffuse nuclear staining for TLE1?

Biphasic synovial sarcoma
Monophasic synovial sarcoma
Poorly differentiated synovial sarcoma
All of the above
None of the above

Board review answer #2

D. All of the above

Board review style question #3

Which of the following translocations is associated with synovial sarcoma?

t(2;5)
t(11;22)
t(14;18)
t(17;22)
t(X;18)

Board review answer #3

E. t(X;18)