Stains & molecular markers
Transducin-like enhancer of split 1 (TLE1)
Copyright: 2018-2021, PathologyOutlines.com, Inc.
PubMed Search: "Transducin-like enhancer of split 1" OR TLE1[TI]
Transducin-like enhancer of split 1 (TLE1)
Authors: Anna Dusenbery, M.D., Mark R. Wick, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 1 March 2018
Minor changes: 7 December 2020
Copyright: 2018-2021, PathologyOutlines.com, Inc.
PubMed Search: "Transducin-like enhancer of split 1" OR TLE1[TI]
Table of Contents
Definition / general | Clinical relevance | Uses in diagnostic anatomic pathology | Laboratory considerations | Microscopic (histologic) images | Positive staining - normal tissues | Positive staining - pathologic conditions | Negative staining | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2 | Board review style question #3 | Board review style answer #3Cite this page: Dusenbery A. Transducin-like enhancer of split 1 (TLE1). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainstle1.html. Accessed January 17th, 2021.
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
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
- 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 style 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 style 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 style answer #3
E. t(X;18)
