title: Platelet-derived growth factor-alpha receptor expression supports the growth of conventional chondrosarcoma and is associated with adverse outcome.
abstract: Bone cells are important targets of platelet-derived growth factors (PDGFs) because they stimulate proliferation of osteoblasts and chondrocytes. In this study we wanted to determine the expression of PDGF-AA and PDGF-alpha receptor in conventional chondrosarcomas and to compare the results with those obtained from benign enchondromas and non-neoplastic cartilage tissue. Sixty-seven chondrosarcomas, 20 enchondromas, and 5 specimens of healthy cartilage as well as 7 specimens of hypertrophic callus cartilage were immunohistochemically analyzed for the expression of PDGF-AA and PDGF-alpha receptor, respectively. Additionally, the proliferation activity was examined with the MIB-1 antibody. Clinical follow-up data were available from 53 patients. A significant overexpression of receptor and factor was found in chondrosarcomas as compared with enchondromas (PDGF-AA p = 0.013, PDGF-alpha receptor p <0.001). MIB-1 values were significantly higher in chondrosarcomas (p <0.001). In healthy joint cartilage no staining was detectable, whereas reactive cartilage of callus formation showed high expression levels. PDGF-alpha receptor expression was significantly higher in grade 3 chondrosarcomas compared with grade 2 (p = 0.022) and grade 1 tumors (p = 0.002). Survival analysis documented a significantly shorter overall survival for patients with high PDGF-alpha receptor expression (p = 0.0172, log-rank test). Because PDGF-alpha receptor expression positively correlates with the aggressiveness of chondrosarcoma, it may be considered as a possible target for novel therapeutic strategies.
authors.affiliation: Department of Clinical Pathology, University of Vienna Medical School, Vienna, Austria. irene.sulzbacher@akh-wien.ac.at
authors.forename: I
authors.initials: I
authors.lastname: Sulzbacher
authors.forename: P
authors.initials: P
authors.lastname: Birner
authors.forename: K
authors.initials: K
authors.lastname: Trieb
authors.forename: M
authors.initials: M
authors.lastname: Mühlbauer
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: A
authors.initials: A
authors.lastname: Chott
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002146:Bony Callus / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D002812:Chondroma / Q000378:metabolism / Q000473:pathology; D002813:Chondrosarcoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha