Vessel Density, Proliferation, and Immunolocalization of Vascular Endothelial Growth Factor in Juvenile Nasopharyngeal Angiofibromas

Abstract

Background: Juvenile nasopharyngeal angiofibroma (JNA) is a rare, highly vascularized neoplasm of the nasopharynx that affects boys and young men. The underlying dysregulated molecular mechanisms remain unclear. The participation of angiogenic growth factors has been suggested, but few studies have been published. Objectives: To evaluate the expression and localization of vascular endothelial growth factor (VEGF), proliferating cells, and vessel density in JNA. Study Design: Immunohistochemical examination of 10 consecutive JNAs (8 primary tumors and 2 recurrent tumors). Methods: Paraffin-embedded and cryopreserved JNA samples were included. VEGF-, CD31-, and Ki67specific antibodies were applied and visualized using light microscopy. Vascularization was determined by counting CD31-positive vessels. Proliferating and VEGFexpressing vessels as well as stromal cells were quantified by the same method. Patients' age at the time of surgery and tumor stage were correlated with the immunohistochemical data. Results: All tumors were heavily vascularized, but major differences were noted between the samples. About half of the vessels were proliferating (Ki67 positive) and half of the Ki67-positive cells were also VEGF positive. The tumor stroma was VEGF positive in 8 of 10 samples and proliferating in 5 of these 8. The 5 samples with both VEGF-and Ki67-positive stroma showed high vessel densities. No correlation was observed between age or tumor stage and vessel density, VEGF expression, or Ki67 expression. Conclusions: In JNA, VEGF is frequently expressed by stromal cells and vessels and is associated with proliferation and increased vessel density. We suggest the promotion of vascularization by VEGF, but the involvement of androgens in JNA angiogenesis still needs to be analyzed.

Differential Gene Expression and Pathway Analysis in Juvenile Nasopharyngeal Angiofibroma Using RNA Sequencing

“…Downstream mediators of VEGF indicate pronounced activation of this pathway ( Table 2 ). These findings support previous studies implicating VEGF activity in disease progression 12 …”

Hypoxia-Inducible Factor-1α (HIF-1α) Expression on Endothelial Cells in Juvenile Nasopharyngeal Angiofibroma: A Review of 70 cases and Tissue Microarray Analysis

“…Tumors with more vessels tend to bleed and are therefore discovered earlier, and tumor size and extension are not necessarily greater than those in tumors with fewer vessels. This is in line with the observations of Brieger et al, 6 who found no correlation between stage and vessel density or VEGF.…”

Anti-human Vascular Endothelial Growth Factor (VEGF) Antibody Selection for Immunohistochemical Staining of Proliferating Blood Vessels

“…Both were clearly positive in VMs with immature capillary proliferation, whereas in more-mature VMs without proliferation, both VEGF and Ki67 were fully absent (Figures 6C and 6D). This observation clearly fits with the concept that VEGF acts as a powerful mitogen for endothelial cells (Ferrara et al 2003; Brieger et al 2004). A good correlation between VEGF and cell proliferation has also been described in neoplasms by Takahashi et al (1995) and Brieger et al (2004).…”