Smoothelin

Smoothelin is a cytoskeletal protein specific to contractile smooth muscle.  There are two isoforms.  The short isoform (A) is highly expressed in visceral smooth muscle. The long isoform (B) is exclusively expressed by vascular smooth muscle cells.  Expression by myofibroblasts is limited and it is absent from myoepithelial cells and from striated smooth muscle.  It is only expressed by smooth muscle at the contractile terminally differentiated stage.

Immunohistochemical expression

In the bladder, expression is largely restricted to the muscularis propria with near absence from the muscularis mucosae.  In the gastro-intestinal tract, there is strong expression buy the muscularis propria.  The muscularis mucosae shows strong expression in the oesophagus, moderate staining in the stomach and weak staining in the intestines.

  Bladder muscle staining Smoothelin SMA Actin (HUC1-1) Caldesmon Desmin Vimentin CD10  
               
Myofibroblasts reactive to carcinoma 0/152 15/152 8/152 0/152 0/152 15/152 11/152
smooth muscle of muscularis propria 15/152, 42/423, 24/244 15/152, 42/423 15/152 15/152 15/152 1/152 0/152
smooth muscle of muscularis mucosae 7/112 , 23/423, 10/184 11/112, 42/423 11/112 11/112 11/112 9/112 0/112

moderate or strong staining for smoothelin with negativity or weak staining for vimentin reliably identifies muscularis propria2

The study of problematic transurethral resection specimens, there was overlap in the staining intensity for smoothelin between muscularis mucosae and muscularis propria: interpretation was difficult if smooth muscle of blood vessels or muscularis propria was not present for comparison with the muscularis mucosae4.

The trigone has muscularis propria extending superficially with a gradual diminution in the size of smooth muscle bundles; these show less staining than does the deeper muscularis propria.  At the ureteric insertions, ureteric muscularis propria is present superficially and is positive for smoothelin3.  

 

    cytoplasmic and nuclear staining exclusively nuclear staining  
Gastrointestinal mural leiomyoma 11/111 0/111
Leiomyoma of gastrointestinal muscularis mucosae 13/131 0/131
Gastrointestinal leiomyosarcoma low grade 1/31 1/31
high grade 3/141 6/141
Gastrointestinal stromal tumour spindle cell 0/261 2/261
epithelioid 0/151 5/151
mixed 0/131 5/131
Gastric Schwannoma 0/121 0/121
Inflammatory myofibroblastic tumour 0/151 0/151
Mesenteric desmoid fibromatosis 0/91 0/91
Dedifferentiated liposarcoma 0/101 0/101
Malignant peripheral nerve sheath tumour 0/91 0/91
       

Diagnostic utility

References

1 Coco DP, Hirsch MS, Hornick JL. Smoothelin is a specific marker for smooth muscle neoplasms of the gastrointestinal tract. Am J Surg Pathol. 2009 Dec;33(12):1795-801.

2 Council L, Hameed O. Differential expression of immunohistochemical markers in bladder smooth muscle and myofibroblasts, and the potential utility of desmin, smoothelin, and vimentin in staging of bladder carcinoma. Mod Pathol. 2009 May;22(5):639-50.

3 Paner GP, Shen SS, Lapetino S, Venkataraman G, Barkan GA, Quek ML, et al. Diagnostic utility of antibody to smoothelin in the distinction of muscularis propria from muscularis mucosae of the urinary bladder: a potential ancillary tool in the pathologic staging of invasive urothelial carcinoma. Am J Surg Pathol. 2009 Jan;33(1):91-8.

4 Miyamoto H, Sharma RB, Illei PB, Epstein JI. Pitfalls in the use of smoothelin to identify muscularis propria invasion by urothelial carcinoma. Am J Surg Pathol. 2010 Mar;34(3):418-22.

 

This page last revised 18.3.2010.

©SMUHT/PW Bishop