title: Molecular characterization of synovial sarcoma in children and adolescents: evidence of akt activation.
abstract: Synovial sarcoma (SS) is the most frequent nonrhabdomyosarcomatous soft tissue sarcoma encountered in adolescents and young adults, and despite advances in the treatment of local disease, metastases remain the main cause of death. The aim of this study was to characterize a single-center series of pediatric SS molecularly to seek any biomarkers or pathways that might make suitable targets for new agents. Seventeen cases of pediatric SS showing the SYT-SSX fusion transcript were screened immunohistochemically, biochemically, molecularly, and cytogenetically (depending on the available material) to investigate any expression/activation of epidermal growth factor receptor, platelet-derived growth factor receptor alpha (PDGFRalpha), PDGFRbeta, Akt, and deregulated Wnt pathway. The most relevant outcome was the finding of activated epidermal growth factor receptor, PDGFRalpha, and PDGFRbeta, which activated Akt in both the monophasic and biphasic histologic subtypes. Consistently, Akt activation was completely abolished in an SS cell line assay when stimulated by PDGF-AA and treated with the phosphatidylinositol 3-kinase inhibitor LY294002. Our results also showed the nuclear localization of beta-catenin and cyclin D1 gene products in monophasic SS and the movement of beta-catenin into the cytoplasm in the glandular component of the biphasic subtype. Although they need to be confirmed in larger series, these preliminary data suggest that therapeutic strategies including specific inhibitors of the phosphatidylinositol 3-kinase/Akt pathway might be exploited in SS.
authors.affiliation: Experimental Molecular Pathology, Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bozzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Tiziana
authors.initials: T
authors.lastname: Negri
authors.forename: Elena
authors.initials: E
authors.lastname: Conca
authors.forename: Da Riva
authors.initials: da R
authors.lastname: Luca
authors.forename: Marco
authors.initials: M
authors.lastname: Losa
authors.forename: Paola
authors.initials: P
authors.lastname: Casieri
authors.forename: Marta
authors.initials: M
authors.lastname: Orsenigo
authors.forename: Andrea
authors.initials: A
authors.lastname: Lampis
authors.forename: Cristina
authors.initials: C
authors.lastname: Meazza
authors.forename: Michela
authors.initials: M
authors.lastname: Casanova
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti