title: Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67.
abstract: To determine various clinical, radiographic, and pathological parameters which may indicate an increased risk of Giant cell tumour of bone (GCTB) recurrence after surgical therapy.
  
  
  
  The study included a total of 164 GCTB samples; 118 (72 %) primary tumours, and 46 (28 %) recurrences; which were analyzed on immunohistochemistry for expression of Ki67, p53, cyclin D1, and β-catenin.
  
  
  
  Among 13 analyzed clinical, radiological, and histological variables, which presented possible predictive factors for the incidence of GCTB relapse, univariate logistic regression (ULR) extract three highly statistically significant parameters: 1) lesion localization, 2) nuclear p53 expression in mononuclear cells, and 3) nuclear cyclin D1 expression in giant multinuclear cells. The multivariate logistic regression (MLR), revealing that p53 expression in mononuclear cells was the most significant predictive factor (HR = 6,181 p < 0,001), the positivity of which indicated six times higher probability for recurrence in GCTB. The expression of cyclin D1 in giant cells, containing less than 15 nuclei, was also statistically significant (HR = 8,398, p = 0,038) for predicting the recurrence, and demonstrated eight times more frequent recurrence in positive tumours.
  
  
  
  This study confirmed independent predicting factors for GCTB reccurence: p53 expression in mononuclear tumour cells and cyclin D1 expression in giant multinuclear cells. Results are new addition to generally known parameters, such as: localization of lesion, number of surgical interventions, clear destruction of cortex with the presence of extracompartmental lesion, and histological criteria for malignancy and can help in further research and treatment of GCTB.
authors.affiliation: Institute for Orthopedic Surgery "Banjica", School of Medicine, University of Belgrade, M. Avramovica St. 28, 11000, Belgrade, Serbia.
authors.forename: Nenad
authors.initials: N
authors.lastname: Lujic
authors.affiliation: Institute for Pathology, Medical Faculty, School of Medicine, University Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Sopta
authors.affiliation: Institute for Pathology, Medical Faculty, School of Medicine, University Belgrade, Dr Subotica 1, 11000, Belgrade, Serbia.
authors.forename: Relja
authors.initials: R
authors.lastname: Kovacevic
authors.affiliation: Institute for Orthopedic Surgery "Banjica", School of Medicine, University of Belgrade, M. Avramovica St. 28, 11000, Belgrade, Serbia. drvladanstevanovic@gmail.com.
authors.forename: Vladan
authors.identifier: 0000-0003-3843-152X
authors.initials: V
authors.lastname: Stevanovic
authors.affiliation: Institute of Nuclear Sciences "Vinča", University of Belgrade, Mike Alasa 12-14, 11000, Belgrade, Serbia.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Davidovic
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000601:surgery; D019938:Cyclin D1 / Q000096:biosynthesis*; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D012042:Registries; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019938:Cyclin D1
keywords: Cyclin D1; Giant cell tumour of bone; Recurrence; p53