Markers of vascular differentiation, proliferation and tissue remodeling in juvenile nasopharyngeal angiofibromas

Nonogaki,Suely; Campos,Heloisa   G.A.; Butugan,Ossamu; Soares,Fernando   A.; Rotea Mangone,Flávia Regina; Torloni,Humberto; Mitzi Brentani,M.

doi:10.3892/etm.2010.141

Markers of vascular differentiation, proliferation and tissue remodeling in juvenile nasopharyngeal angiofibromas

Authors:
- Suely Nonogaki
- Heloisa G.A. Campos
- Ossamu Butugan
- Fernando A. Soares
- Flávia Regina Rotea Mangone
- Humberto Torloni
- M. Mitzi Brentani
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Affiliations: Instituto Adolfo Lutz, Central, Divisão de Patologia, Laboratório de Imuno-histoquímica, CEP 01246-902, São Paulo, Brasil, Hospital A.C. Camargo, CEP 01509-010, São Paulo, Brasil, Departamento de Oftalmologia e Otorrinolaringologia, Faculdade de Medicina da Universidade de São Paulo, Cerqueira César CEP 05403-010, São Paulo, Brasil, Departamento de Radiologia e Oncologia, Disciplina de Oncologia, Faculdade de Medicina da Universidade de São Paulo (LIM-24), CEP 01246-903, São Paulo, Brasil
Published online on: August 26, 2010 https://doi.org/10.3892/etm.2010.141
Pages: 921-926

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Abstract

Juvenile nasopharingeal angiofibroma (JNA) is a histologically benign locally aggressive tumor characterized by irregular vessels embedded in a fibrous stroma. Excessive vascularity results in bleeding complications, and the inhibition of angiogenesis is a promising strategy for managing extensive JNA tumors. To better characterize the endothelial components of JNA, we aimed to evaluate markers of vascular differentiation and proliferation, such as friend leukemia integration-1 (FLI-1) and endoglin, lymphatic markers, including podoplanin and vascular endothelial growth factor receptor 3 (VEGFR3) and its cognate ligand VEGFC, GLUT-1, a diagnostic marker that discriminates between hemangiomas and vascular malformations, and two markers of tissue remodeling, stromelysin 3 (ST3) and secreted acid protein rich in cysteine (SPARC). Antigens were assessed immunohistochemically in vessels and stromal cells of JNA archival cases (n=22). JNA endothelial cells were positive for endoglin, VEGFC and FLI-1, whereas podoplanin and VEGFR3 were negative in all cases. Both endothelial cells and fibroblasts stained for ST3 and SPARC. GLUT-1 was investigated in JNA cases, in infantile hemangiomas (n=123) and in vascular malformations (n=135) as controls. JNAs and vascular malformations were GLUT-1-negative, while hemangiomas showed positive staining. The presence of markers of endothelial differentiation and proliferation highlighted the hyper-proliferative state of JNA vessels. The absence of podoplanin and VEGFR3 underscores their blood endothelial cell characteristic. The absence of GLUT-1 discriminates JNAs from hemangiomas. ST3 and SPARC up-regulation in endothelial cells and fibroblasts may contribute to a compensatory signaling for controlling angiogenesis. Some of these markers may eventually serve as therapeutic targets. Our results may aid in the understanding of JNA pathophysiology.

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