title: Prognostic relevance of CCN3 in Ewing sarcoma.
abstract: Ewing sarcoma is a highly aggressive malignant bone tumor occurring preferentially in children and young adults. At present, only clinical features, such as patient age, presence of clinically evident metastases at diagnosis, and poor response to neoadjuvant chemotherapy, are widely accepted as prognostic indicators in Ewing sarcoma. In this study, we assessed the prognostic value of CCN3 (Nov), a matricellular protein that play crucial roles in bone formation. Polyclonal antibodies directed against each of the different CCN3 modules were used to identify variant CCN3 proteins in tumors and to draw potential relationships between the expression of these variants and the outcome of patients with Ewing sarcoma. Our results confirmed that expression of the full-length CCN3 in Ewing sarcoma is associated to a worse prognostic. Furthermore, we report a possible relationship between the expression of a CCN3 protein lacking an internal module (von Willebrand factor type C) and sensitivity to radiotherapy. We hypothesize that the increased level of variant CCN3 in the tumor cells reduces their tumorigenic potential and results in better outcome.
authors.affiliation: Rizzoli Orthopaedic Institute, Bologna, Italy. bperbal@gmail.com
authors.forename: Bernard
authors.initials: B
authors.lastname: Perbal
authors.forename: Noureddine
authors.initials: N
authors.lastname: Lazar
authors.forename: Diana
authors.initials: D
authors.lastname: Zambelli
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Lopez-Guerrero
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D055514:Nephroblastoma Overexpressed Protein / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012512:Sarcoma, Ewing / Q000235:genetics / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C526319:CCN3 protein, human; D055514:Nephroblastoma Overexpressed Protein