Top

International Orthopaedics

Published in:

01-11-2016 | Original Paper

Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67

Authors: Nenad Lujic, Jelena Sopta, Relja Kovacevic, Vladan Stevanovic, Radoslav Davidovic

Published in: International Orthopaedics | Issue 11/2016

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Errani C, Ruggieri P, Asenzio MA (2010) Giant cell tumor of the extremity: a review of 349 cases from a single institution. Cancer Treat Rev 36:1–7CrossRefPubMed

Yasko AW (2002) Giant cell tumor of bone. Curr Oncol Rep 4:520–526CrossRefPubMed

Domovitov SV, Healey JH (2010) Primary malignant giant-cell tumor of bone has high survival rate. Ann Surg Oncol 17:694–701CrossRefPubMed

Mendenhall WM, Zlotecki RA, Scarborough MT, Gibbs CP, Mendenhall NP (2006) Giant cell tumor of bone. Am J Clin Oncol 29:96–99CrossRefPubMed

Raskin KA, Schwab JH, Mankin HJ, Springfield DS, Hornicek FJ (2013) Giant cell tumor of bone. J Am Acad Orthop Surg 21:118–126CrossRefPubMed

Wulling M, Engels C, Jesse N, Werner M, Delling G, Kaiser E (2001) The nature of giant cell tumor of bone. J Cancer Res Clin Oncol 127:467–474CrossRefPubMed

Balke M, Schremper L, Gebert C et al (2008) Giant cell tumor of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol 134:969–978CrossRefPubMed

Alberghini M, Kliskey K, Krenacs T et al (2010) Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone. Virchows Arch 456(1):97–103CrossRefPubMed

Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH (2011) Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res 469:591–599CrossRefPubMed

10.

Blackley HR, Wunder JS, Davis AM, White LM, Kandel R, Bell RS (1999) Treatment of giant-cell tumors of long bones with curettage and bone-grafting. J Bone Joint Surg Am 81:811–820CrossRefPubMed

11.

Zhu Z, Zhang C, Zhao S, Dong Y, Zeng B (2013) Partial wrist arthrodesis versus arthroplasty for distal radius giant cell tumours. Int Orthop 37(11):2217–2311CrossRefPubMedPubMedCentral

12.

Turcotte RE, Wunder JS, Isler MH et al (2002) Giant cell tumor of long bone: a Canadian Sarcoma Group study. Clin Orthop Relat Res 397:248–258CrossRef

13.

Niu X, Zhang Q, Hao L et al (2012) Giant cell tumor of the extremity: retrospective analysis of 621 Chinese patients from one institution. J Bone Joint Surg Am 94:461–467CrossRefPubMed

14.

van der Heijden L, Piner SR, van de Sande MA (2016) Pigmented villonodular synovitis: a crowdsourcing study of two hundred and seventy two patients. Int Orthop. doi:10.1007/s00264-016-3208-1 PubMed

15.

Becker WT, Dohle J, Bernd L et al (2008) Local recurrence of giant cell tumor of bone after intralesional treatment with and without adjuvant therapy. J Bone Joint Surg Am 90:1060–1067CrossRefPubMed

16.

Jiang HL, Jiang LM, Han WD (2015) Wnt/β-catenin signaling pathway in lung cancer stem cells is a potential target for the development of novel anticancer drugs. J BUON 20(4):1094–100PubMed

17.

Rousseau MA, Luca AH, Lazennec JV (2004) Metachronous multicentric giant cell tumor of the bone in the lower limb. Case report and Ki 67 immuno-histochemistry study. Virchows Arch 445:79–82PubMed

18.

Kandel R, Li SQ, Bell R et al (2006) Cyclin D1 and p21 is elevated in the giant cells of giant cell tumors. J Orthop Res 24(3):428–37CrossRefPubMed

19.

Matsubayashi S, Nakashima M, Kumagai K et al (2009) Immunohistochemical analyses of beta-catenin and cyclin D1 expression in giant cell tumor of bone (GCTB): a possible role of Wnt pathway in GCTB tumorigenesis. Pathol Res Pract 205(9):626–33CrossRefPubMed

20.

Okubo T, Saito T, Mitomi H et al (2013) p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1. Virchows Arch 463(1):67–77CrossRefPubMed

21.

Chakarun CJ, Forrester DM, Gottsegen CJ, Patel DB, White EA, Matcuk GR Jr (2013) Giant cell tumor of bone: review, mimics, and new developments in treatment. Radiographics 33:197–211CrossRefPubMed

22.

Popovic KS, Lukic S, Popovic P (2014) Pretreatment perfusion CT and CT volumetry in squamous cell carcinoma of the head and neck region. J BUON 19(4):937–43PubMed

23.

Cowan RW, Singh G (2013) Giant cell tumor of bone: a basic science perspective. Bone 52:238–246CrossRefPubMed

24.

Scully SP, Mott MP, Temple HT, O’Keefe RJ, O’Donnell RJ, Mankin HJ (1994) Late recurrence of giant-cell tumor of bone. A report of four cases. J Bone Joint Surg Am 76:1231–1233PubMed

25.

de Souza PE, Paim JF, Carvalhais JN, Gomez RS (1999) Immunohistochemical expression of p53, MDM2, Ki-67 and PCNA in central giant cell granuloma and giant cell tumor. J Oral Pathol Med 28(2):54–58CrossRefPubMed

26.

Prosser GH, Baloch KG, Tillman RM, Carter SR, Grimer RJ (2005) Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone. Clin Orthop Relat Res 435:211–218CrossRef

27.

Wang HC, Chien SH, Lin GT (2005) Management of grade III giant cell tumors of bones. J Surg Oncol 92:46–51CrossRefPubMed

28.

Wadayama B, Toguchida J, Yamaguchi T, Sasaki MS, Yamamuro T (1993) p53 expression and its relationship to DNA alterations in bone and soft tissue sarcomas. Br J Cancer 68(6):1134–1139CrossRefPubMedPubMedCentral

29.

Levine AJ, Perry ME, Chang A et al (1994) The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer 69(3):409–416CrossRefPubMedPubMedCentral

30.

Toguchida J, Yamaguchi T, Ritchie B et al (1992) Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. Cancer Res 52(22):6194–6199PubMed

31.

Wang H, Wan N, Hu Y (2012) Giant cell tumour of bone: a new evaluating system is necessary. Int Orthop 36(12):2521–7CrossRefPubMedPubMedCentral

Title: Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67
Authors: Nenad Lujic
Jelena Sopta
Relja Kovacevic
Vladan Stevanovic
Radoslav Davidovic
Publication date: 01-11-2016
Publisher: Springer Berlin Heidelberg
Published in: International Orthopaedics / Issue 11/2016
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI: https://doi.org/10.1007/s00264-016-3292-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Recurrence of giant cell tumour of bone: role of p53, cyclin D1, β-catenin and Ki67

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2016

Treatment of displaced supracondylar humeral fractures in children by humero-ulnar external fixation

Anatomical principles for minimally invasive reconstruction of the acromioclavicular joint with anchors

Surgical treatment for osteoporotic thoracolumbar vertebral collapse using vertebroplasty with posterior spinal fusion: a prospective multicenter study

Open reduction and internal fixation of three- and four-part proximal humeral fractures by intra-focal distraction: observational study of twenty five cases

The focally constrained liner is a reasonable option for revision of unstable total hip arthroplasty

Surgical versus conservative treatment of primary patellar dislocation. A systematic review and meta-analysis