title: Wnt pathway, angiogenetic and hormonal markers in sporadic and familial adenomatous polyposis-associated juvenile nasopharyngeal angiofibromas (JNA).
abstract: Juvenile nasopharyngeal angiofibroma (JNA) is a rare, invasive, and locally destructive tumor of the nasopharynx. The Wnt pathway, angiogenetic and hormonal factors are involved in the pathophysiology of JNA; it can result in an extracolonic manifestation of familial adenomatous polyposis (FAP) or in a sporadic tumor. All patients who underwent resection of JNA between 1991 and 2006 at the University of Modena and Reggio Emilia were studied to identify immunohistochemical markers of associated FAP syndrome. Paraffin-embedded JNA samples were analyzed immunohistochemically for the expression of adenomatous polyposis coli (APC), beta-catenin, E-cadherin, androgen receptor, and vascular endothelial growth factors receptor (VEGFR2). In one out of the 4 (25%) young patients affected by JNA the diagnosis of FAP syndrome linked to APC mutation was made. All of the sporadic and familial JNA tumors showed nuclear staining of beta-catenin, whereas altered APC expression was seen only in FAP-associated JNA. All cases were stained with VEGFR2. A combined clinical, immunohistochemical, and biomolecular screening may be useful for the identification of FAP among patients with a diagnosis of JNA. The Wnt pathway can be involved in the JNA pathogenesis either by somatic mutations of beta-catenin or by germline APC mutations. As the VEGFR has an important impact on the pathogenesis of JNA, we suggest that a targeted therapy with monoclonal antibodies against VEGFR might lead to a specific chemoprevention and treatment of these tumors and their recurrences.
authors.affiliation: Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy. ponti.giovanni@unimo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Rossi
authors.forename: Livio
authors.initials: L
authors.lastname: Presutti
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattioli
authors.forename: Domenico
authors.initials: D
authors.lastname: Villari
authors.forename: Luciano
authors.initials: L
authors.lastname: Wannesson
authors.forename: Matteo
authors.initials: M
authors.lastname: Alicandri Ciufelli
authors.forename: Paola
authors.initials: P
authors.lastname: Izzo
authors.forename: Marina
authors.initials: M
authors.lastname: De Rosa
authors.forename: Pietro
authors.initials: P
authors.lastname: Marone
authors.forename: Stefania
authors.initials: S
authors.lastname: Seidenari
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D018322:Angiofibroma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D011944:Receptors, Androgen; D051153:Wnt Proteins; D051176:beta Catenin; D040262:Receptors, Vascular Endothelial Growth Factor