TLE1, Transducin-Like Enhancer of split 1

TLE1 is one of four transducer-like enhancer genes. It is homologous with the Drosophila groucho gene.  TLE genes are transiently expressed during embryogenesis. It id involved in the control of haemopoiesis, neuronal differentiation and terminal epithelial differentiation.  TLE1 competes with butacaine to form TLE1-TCF/LEF complexes.

The Wnt signalling pathway is strongly associated with synovial sarcoma. TLE1 is a gene related to this pathway and has been shown to be differentially expressed in synovial sarcoma in gene microarray expression studies.

Immunohistochemical expression

Staining is nuclear. Monoclonal (anti-pan-TLE) and polyclonal (M101) antibodies have been raised and have shown similar results, the monoclonal antibody being somewhat more sensitive but less specific1. The threshold for positivity has been taken as at least 10% or nuclei showing intense staining or at least 50% of nuclei showing well above background staining when assessed with a x10 objective1, and for optimum specificity may be set at 25% of nuclei showing strong nuclear staining2. Other antigens used in the diagnosis of synovial sarcoma are shown for comparison.

In non-neoplastic tissues, occasional nuclear positivity may be seen in basal keratinocytes, adipocytes, perineural cells, endothelial cells and mesothelial cells.

 

 

TLE1

 AE1/AE3 EMA bcl-2  

Synovial sarcoma

91/941, 35/352, 18/203

 24/352 18/352 30/352  

Haemangiopericytoma

2/51

        

Schwannoma

5/161, 0/12, 11/113

 0/12 0/12 1/12  

Cellular Schwannoma

1/61

        

Neurofibroma

3/93

        

Solitary fibrous tumour

4/151, 0/32, 2/53

 0/32 1/32 2/32  

Fibroxanthoma

1/41

        

Carcinosarcoma

1/71

        

Clear cell sarcoma

1/71, 0/13

        

Chondrosarcoma, high grade

1/81

        

Ewing sarcoma

1/131, 0/22

 0/22 1/22 1/22  

Gastrointestinal stromal tumour

2/351, 0/63

        

MPNST

3/881, 1/432, 6/103

 7/432 3/432 11/432  

Leiomyosarcoma

1/411, 1/53

        

Angiosarcoma

0/131

        

Breast carcinoma

0/21

        

Chondroblastoma

0/41

        

Chondromyxoid fibroma

0/21

        

Chondrosarcoma, low grade

0/231

        

Chondrosarcoma, myxoid

0/71

        

Chondrosarcoma, mesenchymal

0/21

        

Dermatofibrosarcoma protuberans

0/171

        

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation

0/52

0/52

 0/52 1/52  

DSRCT

0/31, 0/13

        

Enchondroma

0/41

        

Endometrial stromal sarcoma

0/111

        

Epithelioid sarcoma

0/21

        

Fibromatosis

0/171, 0/12

        

Fibrosarcoma

0/31, 1/12, 0/33

 0/12 0/12 0/12  

Giant cell tumour of tendon sheath

0/91

        

Glomus tumour

0/71

        

Granular cell tumour

0/81

        

Vascular tumour

0/91

        

Inflammatory myofibroblastic tumour

0/31

        

Kaposi sarcoma

0/21

        

Leiomyoma

0/81

        

Lipoma

3/83

        

Lipoblastomatosis

0/21

        

Liposarcoma

12/243

        

Liposarcoma, dedifferentiated

0/141

        

Liposarcoma, myxoid

0/41

        

Liposarcoma, pleomorphic

0/21

        

Liposarcoma, well differentiated

0/111

        

MFH

0/561

        

Melanoma

0/111

        

Myxofibrosarcoma, low grade

0/51, 0/22, 0/13

 1/22 0/22 1/22  

Myxoma

0/81

        

Myxosarcoma

0/41

        

Neurofibroma, diffuse

0/121

        

Neurofibroma, localised

0/81

        

Neurofibroma, plexiform

0/241

        

Osteosarcoma

0/161

        

Perineuroma

0/41

        

Rhabdomyosarcoma

0/131, 0/12, 5/133

 0/12 0/12    

Small round cells tumour consistent with alveolar rhabdomyosarcoma

0/12

 0/12 0/12 1/12  

Sarcoma, NOS

0/71, 0/22

 0/22 1/12    
Pleomorphic sarcoma, NOS 1/12 0/12 0/12 1/12  
High grade sarcoma with epithelioid features 0/12 0/12 0/12    
Low grade myofibroblastic sarcoma 0/12 0/12 0/12 0/12  
Small round cell tumour consistent with mesenchymal chondrosarcoma 0/12 0/12 0/12    
Mesothelioma 0/22 1/22      
Spindle cell carcinoma 0/22 1/22 0/22 0/22  
MFH 0/12 0/12 0/12 0/12  
Nodular fasciitis 0/12 0/12 0/12 0/12  
Alveolar soft part sarcoma 0/23        
Acral myxoinflammatory fibroblastic sarcoma 1/13        
Chordoma 1/103        
Parachordoma/myoepithelioma 0/33        
Ewing sarcoma 0/43        
Endometrial stromal sarcoma 3/33        
Epithelioid sarcoma 2/63        
Fibroma 0/23        
Undifferentiated pleomorphic sarcoma 2/123        
Myxofibrosarcoma 1/33        
           

Diagnostic utility

Diagnosis of synovial sarcoma.  It is claimed to have superior sensitivity and specificity by comparison with EMA, bcl-2 and AE1/AE32 but this is disputed3.  Specificity may be optimal with the avoidance of aggressive antigen retrieval by heating2.  Negativity for TLE1 may obviate the need for molecular testing2.  If a tumour is consistent with synovial sarcoma and positive for TLE1 but negative for SYT gene breaks by FISH, further probing for cryptic SYT-SSX2 rearrangements should be considered2.

References

1 Terry J, Saito T, Subramanian S, et al. TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol 2007; 31:240-6 Images.  Study using tissue microarray

2 Jagdis A, Rubin BP, Tubbs RR, Pacheco M, Nielsen TO. Prospective evaluation of TLE1 as a diagnostic immunohistochemical marker in synovial sarcoma. Am J Surg Pathol. 2009 Dec;33(12):1743-51.  Study using standard sections

3 Kosemehmetoglu K, Vrana JA, Folpe AL. TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms. Mod Pathol. 2009 Jul;22(7):872-8.  Study using standard sections

 

This page last revised 7.3.2010.

©SMUHT/PW Bishop