Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps: an immunohistochemical study.
BACKGROUND
Juvenile nasopharyngeal angiofibroma is a rare nasopharyngeal tumor that occurs exclusively in adolescent boys. It is a histologically benign but locally persistent growth of stromal and vascular tissue. Although male hormones and some growth factors, such as transforming growth factor beta1 (TGF-beta1), insulin-like growth factor II (IGF-II), and, lately, the proto-oncogene beta-catenin, have been implicated in the histogenesis of the tumor, the biologic signaling pathways that drive this peculiar fibrovascular proliferation are still nuclear.


OBJECTIVE
To evaluate immunoexpressions of beta-catenin, c-Kit, p130Cas, TGF-beta3, bone morphogenic protein 4, nerve growth factor (NGF), and the IGF receptor (IGF-1R) in a series of juvenile nasopharyngeal angiofibromas and to compare to that of a group of nasal polyps.


METHODS
A standard immunohistochemical technique was used on paraffin sections of 12 sporadic juvenile nasopharyngeal angiofibromas and 15 nasal polyps with microwave or steam antigen retrieval. Immunoreactivity was analyzed semiquantitatively in stromal cells and endothelial cells of each case.


RESULTS
The expressions of beta-catenin (nuclear), c-Kit (cytoplasmic), and NGF (cytoplasmic) were higher and more frequent in stromal cells of juvenile nasopharyngeal angiofibromas than those of nasal polyps. Both juvenile nasopharyngeal angiofibromas and nasal polyps showed similarly frequent and strong immunoreactivity for p130Cas and TGF-beta3 and weak immunoreactivity for bone morphogenic protein 4 in both stromal cells and endothelial cells. No IGF-1R immunoreactivity was detected in any case of either group.


CONCLUSIONS
Our results support the role of beta-catenin in juvenile nasopharyngeal angiofibromas and suggest a potential involvement of c-Kit and NGF signaling pathways in the juvenile nasopharyngeal angiofibromas. Although the biologic significance of c-Kit in juvenile nasopharyngeal angiofibromas has yet to be defined, the finding of frequent and high c-Kit expression might have therapeutic importance for patients with juvenile nasopharyngeal angiofibromas.
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA. pjz@mail.med.upenn.edu
Paul J
PJ
Zhang
Randal
R
Weber
Ho-Hi
HH
Liang
Teresa L
TL
Pasha
Virginia A
VA
LiVolsi
D000293:Adolescent; D000328:Adult; D018322:Angiofibroma / Q000737:chemistry* / Q000473:pathology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000276:immunology; D002648:Child; D050719:Crk-Associated Substrate Protein; D006133:Growth Substances / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D009298:Nasal Polyps / Q000737:chemistry* / Q000473:pathology; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000276:immunology; D016612:Paraffin Embedding; D010750:Phosphoproteins / Q000096:biosynthesis / Q000276:immunology; D011506:Proteins; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000276:immunology; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000276:immunology; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000276:immunology; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000276:immunology; D050717:Retinoblastoma-Like Protein p130; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D053782:Transforming Growth Factor beta3
D000954:Antigens, Surface; C493841:BCAR1 protein, human; D019485:Bone Morphogenetic Proteins; D050719:Crk-Associated Substrate Protein; D006133:Growth Substances; C000715470:MAS1 protein, human; D010750:Phosphoproteins; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011980:Receptors, Progesterone; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D020932:Nerve Growth Factor; D019009:Proto-Oncogene Proteins c-kit; D017526:Receptor, IGF Type 1