Immunohistochemical analysis of growth mechanisms in juvenile nasopharyngeal angiofibroma

Abstract

Angiogenic factors are discussed to participate in growth and promotion of juvenile nasopharyngeal angiofibroma (JNA). However, only few data are available and mechanisms remain unclear. In the presented study we analysed the expression and subcellular distribution of several angiogenic growth factors and receptors potentially involved in JNA-growth and -vascularisation. In a retrospective, descriptive, multicenter-study, we analysed 13 formalin-fixed, paraffin-embedded or cryopreserved JNA-tumors (eleven primary tumors and two recurrent ones) after immunohistochemical staining. We used monoclonal antibodies specific for transforming growth factor beta 1 (TGF-beta(1)), basic fibroblast growth factor (bFGF), the VEGF-receptors 1 and -2 (FLT-1 and FLK-1), and the hypoxia inducible factor (Hif-1alpha). Data were compared to the vessel density. Quantitative analysis of staining intensities was performed by a computer assisted quantification technique. Endothelial and stromal compartments of the samples were analysed separately. Data were compared to vessel densities and patients data. The VEGF-Receptor-2 (FLK) was frequently unregulated in the stroma and endothelium of those samples with high vessel densities. Similarly, we observed high bFGF- and TGF-beta(1) levels in the stroma of strong vascularised samples. No correlations of expression levels to patients' data were found. The reported data support the concept of JNA-growth and -vascularisation driven by factors released from stromal fibroblasts. Therefore, inhibition of these factors might be beneficial for the therapy of inoperable JNA.

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

“…Endoglin is a type III/TGFβ1 receptor also up-regulated by TGFβ stimulation (23), and TGFβ type ii receptor gene transcription is activated by Fli-1 (21). TGFβ was previously reported in both the stromal and endothelial cells of JNAs (12,15,16). Taken together, our data emphasize the potential role of TGFβ1 in the pathogenesis of JNA.…”

“…However, such pan endothelium biomarkers did not discriminate between vascular and lymphatic cells, and some are not restricted to blood vessels (10). TGFβ1, FGF, vascular endothelial growth factor (VEGF A) and its receptors, VEGFR1 (Flt-1) and VEGFR2 (kDR), were also reported to be expressed in JNA endothelial cells (11)(12)(13)(14)(15)(16)(17)(18)(19). Of note, several of these growth factors were also elevated in both hemangiomas and in tumor-associated blood vessels (8,20).…”

Biomolecular Analysis of Juvenile Nasopharyngeal Angiofibroma

“…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.…”

Fibroangioma nasofaríngeo juvenil. Experiencia de 15 años en el Hospital Barros Luco Trudeau

“…Aunque histológicamente es benigno, en ocasiones su compleja localización anatómica, su tendencia a la invasión local, la recurrencia y su crecimiento agresivo, hacen que sea un tumor nasosinusal con características peculiares. Ocurre casi exclusivamente en la nasofaringe de adolescentes de sexo masculino 2,3 . Los FNJ tienen un crecimiento lento, centrado en el foramen esfenopalatino y se expanden dentro del la cavidad nasal, nasofaringe y luego en la fosa pterigomaxilar 4 .…”