title: Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas.
abstract: Platelet-derived growth factor (PDGF) receptor signaling has been implicated in the development of glial tumors, but not yet been examined in choroid plexus carcinomas, pediatric tumors with dismal prognosis for which novel treatment options would be desirable. Therefore, protein expression of PDGF receptors alpha and beta as well as amplification status of the respective genes, PDGFRA and PDGFRB, were examined in a series of 22 patients harboring choroid plexus carcinoma using immunohistochemistry and chromogenic in situ hybridization (CISH). The majority of choroid plexus carcinomas expressed PDGF receptors with 6 cases (27%) displaying high staining scores for PDGF receptor alpha and 13 cases (59%) showing high staining scores for PDGF receptor beta. Correspondingly, copy-number gains of PDGFRA were observed in 8 cases out of 12 cases available for CISH and 1 case displayed amplification (six or more signals per nucleus). The proportion of choroid plexus carcinomas with amplification of PDGFRB was even higher (5/12 cases). PDGFRB amplification status and PDGF receptor beta protein expression scores were significantly correlated (P=0.01, Spearman). Expression status of PDGF receptor alpha or PDGF receptor beta was not significantly associated with progression-free survival. To conclude, expression and amplification of PDGF receptors, particularly PDGF receptor beta, are frequent in choroid plexus carcinomas, providing a first rationale for the development of treatments targeting PDGF receptor signaling in these rare malignant pediatric tumors.
authors.affiliation: Molecular Cancer Biology Program, University of Helsinki, Helsinki, Finland.
authors.forename: Nina N
authors.initials: NN
authors.lastname: Nupponen
authors.forename: Janna
authors.initials: J
authors.lastname: Paulsson
authors.forename: Astrid
authors.initials: A
authors.lastname: Jeibmann
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wrede
authors.forename: Minna
authors.initials: M
authors.lastname: Tanner
authors.forename: Johannes E A
authors.initials: JE
authors.lastname: Wolff
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Arne
authors.initials: A
authors.lastname: Ostman
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
mesh_terms: D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002675:Child, Preschool; D016545:Choroid Plexus Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta