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

Abstract

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.

Nasal juvenile angiofibroma: Current perspectives with emphasis on management

“…The cellular, vascular, and locally aggressive tumor that characteristically develops in the posterior nasal cavity of adolescent men is generally referred to as juvenile nasopharyngeal angiofibroma. Because of previous uncertainty regarding the precise origin of the tumor, it has been described using various names in the literature.…”

“…Juvenile angiofibroma is regarded as a benign tumor . Sarcomatous, malignant transformation is extremely rare and attributable to prior radiotherapy (RT) .…”

Biomolecular Analysis of Juvenile Nasopharyngeal Angiofibroma

“…Among these, c-Myc [6,7,28], c-Kit (2,6,7), FLI-1 [5], endoglin [5,11], TNC [9], PCNA [10,12], Ki-67 [16], GSTM1 [17,33], AURKA and MDM2 (34) were shown to be associated with JNA. Among these, GSTM1-null genotype gene seems important.…”

“…Therefore, vascular endothelial growth factor (VEGF), nerve growth factor (NGF), insulin-like growth factor (IGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor (TGF) were assessed in many studies [2,5,6,10,12,[14][15][16]23,[25][26][27]. The levels of TGF-β1 [10,25,27,29], basic fibroblast growth factor (bFGF) [6,15,25,26], NGF (2), and VEGF [5,6,10,12,14,16,23,25] were found to be elevated in JNA. The most notable of which are TGF-β1 and VEGF.…”

“…protooncogenes, including p53, c-Myc, H-Ras, Ki-Ras, c-Kit, p130Cas, Friend leukemia integration-1 (FLI-1), endoglin, podoplanin, stromelysin-3 (ST3), tenascin-C (TNC), syndecan-2, proliferating cell nuclear antigen (PCNA), Bcl-2, Ki-67, S-100, c-Fos, GSTM1 gene, AURKA, MDM2, Her-2/neu, and Hif-1 [2,[5][6][7][9][10][11][12][13][15][16][17]25,27,28,[32][33][34][35], in the etiology of JNA have been investigated. Among these, c-Myc [6,7,28], c-Kit (2,6,7), FLI-1 [5], endoglin [5,11], TNC [9], PCNA [10,12], Ki-67 [16], GSTM1 [17,33], AURKA and MDM2 (34) were shown to be associated with JNA.…”