Immunolocalization of activated transforming growth factor β1 in juvenile nasopharyngeal angiofibroma

Background: Juvenile nasopharyngeal angiofibroma (UNA) is a histologically benign, locally aggressive neoplasm of the nasopharynx that exclusively affects male adolescents. It is known to be sensitive to androgens, but there are likely intermediary cytokines and/or growth factors that mediate aggressive stromal cell proliferation and angiogenesis. Transforming growth factor beta 1 (TGF-beta 1) is a polypeptide that is secreted in an inactive form, cleaved to produce an active form, and then deactivated in the tissues. It activates fibroblast proliferation and is known to induce angiogenesis. Objectives: To evaluate the presence of activated TGF-beta 1 within the stroma of JNA specimens and to quantify the percentage of JNA specimens expressing the active growth factor. Design: Immunohistochemical analysis was performed on 19 specimens of JNA using a unique antibody that identifies only the activated form of TGF-beta 1. The percentage of cells staining positively for activated TGF-beta 1 was determined semiquantitatively by visual methods. Results: Of 19 cases stained, all 19 (100%) showed strong positive staining (2 cases with 33%-66% of cells staining and 17 with 66%-100% of cells staining). Activated TGF-beta 1 was identified in stromal cell nuclei and cytoplasm and in the endothelium of the capillaries within all specimens of JNA. Conclusions: The localization of activated TGF-beta 1 to the fibroblasts and endothelial cells within JNA tumors suggests that TGF-beta 1 may play a role in the stromal cell proliferation and angiogenesis associated with JNA. Additional receptor studies and more quantitative methods of analysis are needed to further define the role of TGF-beta 1 in the pathogenesis of JNA.