title: Markers of vascular differentiation, proliferation and tissue remodeling in juvenile nasopharyngeal angiofibromas.
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.
authors.affiliation: Instituto Adolfo Lutz, Central, Divisão de Patologia, Laboratório de Imuno-histoquímica, CEP 01246-902;
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.forename: Heloisa G A
authors.initials: HG
authors.lastname: Campos
authors.forename: Ossamu
authors.initials: O
authors.lastname: Butugan
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.forename: Flávia Regina Rotea
authors.initials: FR
authors.lastname: Mangone
authors.forename: Humberto
authors.initials: H
authors.lastname: Torloni
authors.forename: M Mitzi
authors.initials: MM
authors.lastname: Brentani