Expression Of Annexin â…¡ And TGF-β₁ Signaling Molecules In Desmoid-Type Fibromatosis

BackgroundDesmoid-type fibromatoses, also known as aggressive fibromatosis, are locally aggressive clonal fibroblastic proliferations that arise in deep soft tissues and are characterized by infiltrative growth and a tendency toward local recurrence, but an inability to metastasise. Treatment of patients with DTF usually involves surgery with the goal of complete local excision of the tumor. Annexinâ…¡is a well established receptor for plasminogen and tissue plasmin activator, and may be a attractive target for anti-breast cancer therapy since it has been shown to bind to angiostatin. No study about the expression of Annexinâ…¡in DTF was found in Pubmed and Wangfang database (1980-2008). TGF-β₁ is a multifunctional protein which plays an important role in cell proliferation, differentiation and apoptosis. It has been found in our previous study that TGF-β₁ may involve inducing transdifferentiaton of fibroblast to myofibroblast and angiogenesis in nodular fasciitis. Although TGF-β₁ expression in DTF has been demonstrated in recent two papers, its role in DTF is still not well known.Objectives:1. To investegate the expression of Annexinâ…¡in DTF and its possible role in DTF.2. To confirm the expression of TGF-β₁ in the DTF, and then to explore its possible role in DTF.Methods:The 34 cases of DTF tumor and matched surrouding tissues were studied byimmunohistochemistry stainings. The expressions of Annexinâ…¡, TGF-β₁/TGF-βRIand VEGF were examined, and the relationship between their expressions andmyofiberblast differentiaton, stroma production and angiogenesis in DTF wasestimated.Results:1. Annexinâ…¡was expressed in 67.6% (29/34) cases of DTF. The expression was markedly in infiltrating region. The average percentage of Annexinâ…¡positive cells (61.34%±11.08%) in DTF was significantly higher than that (19.75%±4.59 %) of surrounding tissues(P<0.05). Within the positive cases of DTF, the average percentage of Annexinâ…¡positive cells in infiltrating areas (65.22%±14.15%) was significantly higher than that in non-infiltrated ones(46.75±9.01)(P<0.05). 2. TGF-β₁ was detected in 79.4%(27/ 34) DTF, with a different expressing level [+ in 29.4% (10/34), ++ in 26.5%(9/34),and +++ in 23.5% (8/34) respectively]. TGF-βRI was detected in 82.3% DTF[+ in 29.4%(10/34), ++ in 23.5% (8/34), and +++ in 29.4% (10/34) respectively]. There was a significant difference between the expression levels of both of TGF-β₁ and TGF-βRI in DTF and those of surrounding tissues (P<0.05) .3. 67.6% (23/34) cases of DTF shownα-SMA positive in the tumor spindle cells [+ in 14.7% (5/34), ++ in 44.1%(15/34), and +++ in 38.8%(3/34)]. There was a positive correlation between the expression level ofα-SMA and that of TGF-βRI in DTF (P<0.05).4. Fibronectin was demonstrated in all cases of DTF. There was a positive correlation between the expression level of fibronectin and that of TGF-βRI in DTF (P<0.05).5. The MVD in DTF was 9.14±2.08.VEGF positive spindle cells and endothelium were found in 88.2%(30/34)DTF. There was a positive correlation between MVD and the average percentage of both VEGF and TGF-β1 positive cellsConclusion:1. There is a overexpression of Annexinâ…¡in DTF. Annexinâ…¡may participated in the development of DTF, possibly in promoting the infiltrative growth of tumour cells by mediating plasminogen activation pathway. Annexinâ…¡reactivity may be the basis of a new attractive target for anti-DTF therapy.2. Overexpressions of both TGF-β₁ and TGF-βRI in DTF indicate that TGF-β₁ may participated in the development of DTF. The results in our study suggest it might envolved in neoplastic myofiberblast differentiaton, stroma production and angiogenesis in DTF.3. VEGF overexpression is present in DTF. Diffuse and strong VEGF reactivity in DTF surggests it may be another target for anti-angiogenic and anti-DTF therapies.