Expression Of Myoid Markers, TGF-β₁ And Related Signaling Molecules In Nodular Fasciitis

Nodular fasciitis, also known, as subcutaneous pseudosarcomatous fasciitis, is amass-forming fibrous proliferation that usually occurs in the subcutaneous tissue. Theetiology and pathogenesis of nodular fascitiis are unknown. Recent cytogeneticstudies have demonstrated clonal chromosomal aberrations in a subset of the lesions,supporting nodular fisciitis as a neoplastic process. With the myofibroblast identifiedand characterized, it becomes apparent that the proliferating cells in nodular fasciitisare composed of fibroblasts and myofibroblasts. Transforming growth factor-β₁ isknown to stimulate fibroblast proliferation and to induce transdifferentiaton offibroblast towards myofibroblast, and has been localized immunohistochemically in awide variety of neoplastic and non-neoplastic tissue. However, there are no studies onthe expression and roles of TGF-β₁ in nodular fasciitis.Objectives:1. To examine the immunoexpression of myoid markers and evaluate themyofibroblastic phenotype in nodular fasciitis.2. To investigate expression and roles of TGF-β₁ and its related signaling moleculesin nodular fasciitis.Methods:The 68 paraffin embedded nodular fasciitis tissues, including the lesion tissues andthe tissues around the lesion, were studied immunohistochemically for the expressionof the following markers: (1) myoid markers: a- smooth muscle actin(a-SMA),muscle special actin(MSA), calponin and h-caldesmon; (2) signaling molecules:TGF-β₁, transforming growth factor-βreceptor typeâ… (TGF-βRI), Smad2 and Smad3.Chi-square test was used to evaluate the expression of TGF-β₁, TGF-βRI, Smad2 andSmad3 between the lesion tissues and the tissues around the lesion. Spearman rank correlation analysis was applied to assess their correlation in these samples.Results:1. The spindled cells in nodular fasciitis showed diffuse or focal immunoreactivityfor a-SMA, MSA and calponin, while h-caldesmon was absent. The positive ratesof a-SMA, MSA and calponin were 89.7ï¼…, 86.8ï¼…and 92.6ï¼…respectively.2. Strong expression of TGF-β₁ and TGF-βRI was demonstrated in the spindle cellsin nodular fasciitis, and week expression in the control. The staining for TGF-β₁and TGF-βRI was found prominently in spindle cell proliferation areas. Thepositive rates of TGF-β₁ and TGF-βRI were 77.9ï¼…and 80.9ï¼…respectively innodular fasciitis, while in the control the positive rates are 30.9ï¼…and 33.8ï¼…respectively. There was a significant difference between nodular fasciitis andperipheral zone reach statistical (P＜0.05), both for the expression of TGF-β₁ andTGF-βRI.3. Strong expression of Smad2 and Smad3 was demonstrated in the spindle ceils innodular fasciitis, and week expression in the control. The positive rates of Smad2and Smad3 were 67.6ï¼…and 61.8ï¼…respectively in nodular fasciitis, while in thecontrol the positive rates were 25.0ï¼…and 20.6ï¼…respectively. There was asignificant differences between nodular fasciitis and the control(P＜0.05), both forthe expression of Smad2 and Smad3.4. There was a positive correlation between the expression of TGF-β₁ and TGF-βRI(P＜0.05), between the expression of TGF-β₁ and Smad2 (P＜0.05), and betweenthe expression of TGF-β₁ and Smad3 (P＜0.05).Conclusions:1. The immunoreactivity for a-SMA, MSA and calponin and absent of reactivity for h-caldesmon in spindle cell of nodular fasciitis indicate the existing ofmyofibroblastic phenotype in the lesion of nodular fasciitis, suggesting that somefibroblasts might be transdifferentiated to myofibroblasts in the development ofnodular fasciitis. Calponin is the most sensitive one for identifyingmyofibroblasts among the above markers. The results in this study alsodemonstrate that nodular fasciitis is not absolutely a lesion predominantlycomposed of myofibroblstic cells.2. TGF-β₁ overexpression noticed in nodular fasciitis might indicate that TGF-β₁participates in the development of nodular fasciitis. It may exert autocrine as wellas paracrine effects on promoting fibroblast proliferation and inducingmyofibroblast transdifferentiation.3. The increased expression of TGF-βRI,Smad2 and Smad3 and their positivecorrelations provide the further evidence that TGF-β₁ may, through TGF-β₁/Smadtransduction pathway, participates in the pathogenesis of nodular fasciitis.