PMID- 20653781 OWN - NLM STAT- MEDLINE DCOM- 20101105 LR - 20151119 IS - 1365-2559 (Electronic) IS - 0309-0167 (Linking) VI - 57 IP - 1 DP - 2010 Jul TI - Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases. PG - 59-72 LID - 10.1111/j.1365-2559.2010.03597.x [doi] AB - AIMS: To identify candidate prognostic biological markers useful in selecting high-risk patients with classic primary giant cell tumours (GCT). GCT specimens with different behaviour associated with an increased risk of local and/or distant relapses were studied. METHODS AND RESULTS: Screening mRNA microarray analysis followed by real-time polymerase chain reaction and immunohistochemistry on tissue microarray sections was used to validate the prognostic role of differentially expressed genes on a larger series by statistical analysis tests. Global gene expression profiling identified 109 differentially expressed genes according to prognosis. A correlation was found between mRNA levels and clinical outcome identifying Tenascin C (TNC) as the most significant prognostic biological marker. By means of backward Wald logistic regression, TNC overexpression defined an eightfold increased risk for metastasis and fourfold for local recurrence. At the protein level, TNC immunoreactivity resulted in a significant difference in the disease-free survival probability curves, providing a stratification for GCT patients, useful for predicting relapse. CONCLUSIONS: Our study provides important data for the selection of biomarkers with a significant clinical impact and suggests the importance of TNC expression in identifying GCT patients at a higher risk of relapse for closer follow-up and adjuvant medical therapy. FAU - Pazzaglia, Laura AU - Pazzaglia L AD - Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, University of Bologna, Bologna, Italy. laura.pazzaglia@ior.it FAU - Conti, Amalia AU - Conti A FAU - Chiechi, Antonella AU - Chiechi A FAU - Novello, Chiara AU - Novello C FAU - Magagnoli, Giovanna AU - Magagnoli G FAU - Astolfi, Annalisa AU - Astolfi A FAU - Pession, Andrea AU - Pession A FAU - Krenacs, Tibor AU - Krenacs T FAU - Alberghini, Marco AU - Alberghini M FAU - Picci, Piero AU - Picci P FAU - Benassi, Maria Serena AU - Benassi MS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Histopathology JT - Histopathology JID - 7704136 RN - 0 (Biomarkers, Tumor) RN - 0 (RNA, Messenger) RN - 0 (RNA, Neoplasm) RN - 0 (Tenascin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Biomarkers, Tumor/genetics/metabolism MH - Bone Neoplasms/*genetics/metabolism MH - Child, Preschool MH - Disease-Free Survival MH - Female MH - Gene Expression MH - Gene Expression Profiling MH - Giant Cell Tumor of Bone/*genetics/metabolism/secondary MH - Humans MH - Immunohistochemistry MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/genetics/metabolism MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/genetics MH - RNA, Neoplasm/genetics MH - Risk Factors MH - Tenascin/*genetics/metabolism MH - Young Adult EDAT- 2010/07/27 06:00 MHDA- 2010/11/06 06:00 CRDT- 2010/07/27 06:00 PHST- 2010/07/27 06:00 [entrez] PHST- 2010/07/27 06:00 [pubmed] PHST- 2010/11/06 06:00 [medline] AID - HIS3597 [pii] AID - 10.1111/j.1365-2559.2010.03597.x [doi] PST - ppublish SO - Histopathology. 2010 Jul;57(1):59-72. doi: 10.1111/j.1365-2559.2010.03597.x.