ABSTRACT
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 have been suggested. The aim of this study is to assess the expression of vasularization and proliferation in the pathogenesis of juvenile nasopharyngeal angiofibroma and to detect the role of antiangiogenic therapy in the treatment. Formalin fixed paraffin embedded sections of fifteen cases of juvenile nasopharyngeal angiofibroma [primary and recurrent] were studied immunohistochemically by VEGF, CD31 and Ki67 specific antibodies and visualized using light microscope. VEGF-expressing vessels, CD31 positive vessels and proliferating cells were evaluated by the same method. All the patients are adolescent males ranging in age between 12 to 26 years. Most tumors examined classified clinically as stage II or III with only one case as stage I and two cases as stage IV. No correlation between patient's age or tumor stage and VEGF expression, vascular density and Ki67 proliferating cells. The number of CD31 positive vessels varied from 15 to 100 per HPF. The microvascular density [MVD] varied from grade 1 to grade 3 in all the studied cases. The number of proliferating cells [ki67proliferating cells] ranged from 12 to 50 per HPF with median count 24, none of the fibroblastic stromal cells showed any reactivity to the CD31 antibodies contrasting the positive staining of the vascular endothelium. The stroma showed 12 cases [80%] with VEGF stromal positivity, while only the rest 3 cases [20%] with VEGF stromal negativity. Also it showed 7 cases [46.6%] with Ki67 positivity while 8 cases [45.4%] with Ki67 negativity. [40% of the studied cases] with positive VEGF stroma showed high vascular count and high MVD [grade 3] while only 4 cases showed low vascular count and low MVD [grade1] and negative stromal VEGF [5cases] showed [grade 2] MVD. [6 cases] with proliferating Ki67 stromal cells showed grade 3 MVD, while only one case with grade 2 MVD. We observed that cases with positive stromal VEGF showed high number of positive VEGF vessels. In JNA, VEGF is frequently expressed by the stromal cells and vessels and is associated with increased vessel density. VEGF is frequently expressed by stromal cells and blood vessels, associated with proliferation and increased vascular density. VEGF contributes to the strong vascularisation of this benign tumor. Therefore, antiangiogenic therapy might be considered. These findings support the theory that nasopharyngeal angiofibroma represents a vasoproliferative malformation