title: Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study.
abstract: Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow-up. The impact of tumor-host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP-2 and to pro-survival proteins NFIB and c-Fos. Kaplan-Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co-overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12-44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor-host endpoints for new biological treatments.
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Quattrini
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pollino
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pazzaglia
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Conti
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Novello
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferrari
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Elettra
authors.initials: E
authors.lastname: Pignotti
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.affiliation: Laboratory of Experimental Oncology, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Benassi
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D016723:Bone Remodeling; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051839:NFI Transcription Factors / Q000502:physiology*; D011379:Prognosis; D053245:RANK Ligand / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D051839:NFI Transcription Factors; C110754:NFIB protein, human; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human
keywords: bone remodeling; giant cell tumor; metastasis; prognostic biomarkers