RESUMO
Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign neoplasm of the nasopharynx that accounts for 0.5% of all head and neck tumors. Although histologically benign in appearance, JNAs are locally aggressive and destructive, spreading from the nasal cavity to the nasopharynx, paranasal sinuses, and orbit skull base with intracranial extension. The gender selectivity of JNA and the relatively young age at diagnosis suggest hormone-dependent development. Hormonal disorders have been reported in patients with JNA, and androgen and estrogen receptors have been identified in tumor tissue; however, a hormonal influence on JNA is controversial. Recent studies have attempted to further delineate the pathogenesis of JNA through analysis of genetic and molecular changes. Understanding of the molecular mechanisms involved in JNA might improve prevention, prognosis, and treatment of this tumor. In this review, we discuss published studies addressing the possible molecular pathways that might be involved in the development of JNA.
Assuntos
Angiofibroma/genética , Neoplasias Nasofaríngeas/genética , Angiofibroma/metabolismo , Criança , Aberrações Cromossômicas , Genes APC , Genes p53 , Glutationa Transferase/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Mutação , Neoplasias Nasofaríngeas/metabolismo , Proto-Oncogenes/genética , RNA Mensageiro/metabolismo , Receptores de Esteroides/metabolismo , beta Catenina/genéticaRESUMO
Biopsies from 25 juvenile nasopharyngeal angiofibromas (JNAs) and respective normal inferior turbinates were examined and compared. The expression patterns of the messenger RNAs (mRNAs) for various growth factors possibly involved in the growth of mesenchymal cells, as well as angiogenesis and fibrosis, were also compared. These growth factors included insulin-like growth factor II (IGF-II), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factors-beta1 (TGF-beta1) and platelet-derived growth factors (PDGF-A and PDGF-B). Quantification of mRNA coding for proto-oncogenes and suppressor genes related to proliferation (i.e., c-myc, c-fos, p53) was also undertaken. Tumor and turbinates expressed similar levels of bFGF, VEGF, TGF-beta1, c-myc, c-fos, and PDGF-A mRNAs. The presence of TGF-beta1 protein was confirmed by immunohistochemistry in several structures that characterize the lesions of JNA, which suggests that TGF-beta1 may play a role in the development of the fibrous component of this tumor. PDGF-B and p53 were overexpressed (i.e., twice the mean level found in turbinates) in 50% and 32% of JNAs, respectively but there was no statistical significance when compared with controls. Statistically significant increased expression of IGF-II mRNA was observed in JNA (P = .04). IGF-II mRNA levels were correlated to p53 (P = .05) and PDGF-B (P = .034), indicating a possible synergistic action of such factors in JNA. The results of this study suggest that IGF-II might be a potential growth regulator of nasopharyngeal angiofibromas.
Assuntos
Angiofibroma/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes p53/genética , Substâncias de Crescimento/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proto-Oncogenes/genética , Adolescente , Adulto , Angiofibroma/genética , Angiofibroma/patologia , Criança , Substâncias de Crescimento/genética , Humanos , Masculino , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Conchas Nasais/patologiaRESUMO
This paper describes the pathobiology of some of the more common skull base tumors. In addition to clinicopathologic features, emphasis is placed upon methods of diagnosis utilizing immunoperoxidase stains and molecular markers that may or may not impact upon prognosis.