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Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study
Author(s) -
Quattrini Irene,
Pollino Serena,
Pazzaglia Laura,
Conti Amalia,
Novello Chiara,
Ferrari Cristina,
Pignotti Elettra,
Picci Piero,
Benassi Maria Serena
Publication year - 2015
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22873
Subject(s) - rankl , medicine , giant cell tumor of bone , bone metastasis , metastasis , osteolysis , tissue microarray , oncology , pathology , cancer , cancer research , immunohistochemistry , giant cell , receptor , surgery , activator (genetics)
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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1205–1211, 2015.