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Journal of Cancer Research and Clinical Oncology

Published in:

01-02-2008 | Original Paper

Livin and Bcl-2 expression in high-grade osteosarcoma

Authors: T. Nedelcu, B. Kubista, A. Koller, I. Sulzbacher, I. Mosberger, F. Arrich, K. Trieb, R. Kotz, C. D. Toma

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2008

Abstract

Aims

The evaluation of prognosis in patients with osteosarcoma is limited to clinical parameters. Although numerous molecular markers have been studied, none are currently in routine clinical use. The aim of this study was to determine if Livin and Bcl-2, acting as antiapoptotic proteins through different mechanisms, are expressed in osteosarcoma, and whether they can be used as prognostic markers in human osteosarcoma.

Methods

Tumor specimens of 29 patients with high-grade central osteosarcoma, with complete clinical follow-up for a minimum of 5 years, were studied. The localization and distribution of Livin and Bcl-2 were investigated using immunohistochemistry. Results were correlated with the histological response to chemotherapy, 5-year disease-free and 5-year overall survival.

Results

Bcl-2 was expressed only in the cytoplasm of 16/29 cases and there was no statistically significant correlation between expression and any of the studied parameters. Livin was detected in 17/29 cases, in the cytoplasm of all 17 and in the nucleus of only 3 cases. Nuclear expression was significantly correlated with a decreased overall survival (P < 0.0002) compared with those patients without nuclear expression.

Conclusions

The results of this study indicate that Bc1-2 and Livin are highly expressed in osteosarcoma cells and that possibly, the evaluation of nuclear Livin expression might be a useful prognostic marker in osteosarcoma.

Bacci G, Picci P, Ferrari S et al (1993) Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities: the recent experience at the Rizzoli Institute. Cancer Treat Res 62:299–308PubMed

Geidel S, Garn M, Gravinghoff L et al (1991) Cardiomyopathy after osteosarcoma treatment: a contribution to the cardiotoxicity of adriamycin. Klin Padiatr 203:257–261PubMedCrossRef

Enneking WF, Spanier SS, Goodman MA (1980) A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop 153:106–120PubMed

Bielack SS, Kempf-Bielack B, Delling G (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20:776–790PubMedCrossRef

Salzer-Kuntschik M, Brand G, Delling G et al (1983) Bestimmung des morphologischen Regressionsgrades nach Chemotherapie bei malignen Knochentumoren. Pathologe 4:135–141PubMed

Winkler K, Beron G, Delling G et al (1988) Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol 6:329–337PubMed

Trieb K, Kotz R (2001) Proteins expressed in osteosarcoma and serum levels as prognostic factors. Int J Biochem Cell Biol 33:11–17PubMedCrossRef

Miller CW, Aslo A, Won A et al (1996) Alterations of the p53, Rp, and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol 122:559–565PubMedCrossRef

Baldini N, Scotlandi K, Barbanti-Brodano G et al (1995) Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med 333:1380–1385PubMedCrossRef

Serra M, Scotlandi K, Reverter-Branchat G et al (2003) Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities. J Clin Oncol 21:536–542PubMedCrossRef

Akatsuka T, Wada T, Kokai Y et al (2002) ErbB2 expression is correlated with increased survival of patients with osteosarcoma. Cancer 94:1397–1404PubMedCrossRef

Gorlick R, Huvos AG, Heller G et al (1999) Expression of HER2/erbB-2 correlates with survival in osteosarcoma. J Clin Oncol 17:2781–2788PubMed

Trieb K, Gerth R, Holzer G et al (2000) Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. Br J Cancer 82:85–87PubMedCrossRef

Trieb K, Lechleitner T, Lang S et al (1998) Heat-shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy. Hum Pathol 29:1050–1055PubMedCrossRef

Uozaki H, Horiuchi H, Ishida T et al (1997) Overexpression of resistance-related proteins (metallothioneins, glutathione-S-transferase pi, heat-shock protein 27, and lung resistance-related protein) in osteosarcoma. Relationship with poor prognosis. Cancer 79:2336–2344PubMedCrossRef

Hussein MR, Haemel AK, Wood GS (2003) Apoptosis and melanoma: molecular mechanisms. J Pathol 199:275–288PubMedCrossRef

Schimmer AD (2004) Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Res 64:7183–7190PubMedCrossRef

Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462PubMedCrossRef

Deveraux QL, Reed JC (1999) IAP family proteins suppressors of apoptosis. Genes Dev 13:239–252PubMed

Ferreira CG, Epping M, Kruyt FA et al (2002) Apoptosis: target of cancer therapy. Clin Cancer Res 8:2024–2034PubMed

Chan SL, Yu VC (2004) Proteins of the Bcl-2 family in apoptosis signalling: from mechanistic insights to therapeutic opportunities. Clin Exp Pharmacol Physiol 31:119–128PubMedCrossRef

Tsujimoto Y (2003) Cell death regulation by the Bcl-2 protein family in the mitochondria. J Cell Physiol 195:158–167PubMedCrossRef

Heiser D, Labi V, Erlacher M et al (2004) The Bcl-2 protein family and its role in the development of neoplastic disease. Exp Gerontol 39:1125–1135PubMedCrossRef

Kasof GM, Gomes BC (2001) Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem 276:3238–3246PubMedCrossRef

Vucic D, Stennicke HR, Pisabarro MT et al (2000) ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol 10:1359–1366PubMedCrossRef

Trieb K, Lehner R, Stulnig T et al (2003) Survivin expression in human osteosarcoma is a marker for survival. Eur J Surg Oncol 29(4):379–82PubMedCrossRef

Ashhab Y, Alian A, Polliack A et al (2001) Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern. FEBS Lett 495:56–60PubMedCrossRef

Gazzaniga P, Gradilone A, Giuliani L et al (2003) Expression and prognostic significance of LIVIN, SURVIVIN and other apoptosis related genes in the progression of superficial bladder cancer. Ann Oncol 14:85–90PubMedCrossRef

Yagihashi A, Asanuma K, Tsuji N et al (2003) Detection of anti-Livin antibody in gastrointestinal cancer patients. Clin Chem 49:1206–1208PubMedCrossRef

Tanabe H, Yagihashi A, Tsuji N et al (2004) Expression of survivin mRNA and Livin mRNA in non-small cell lung cancer. Lung Cancer 46:299–304PubMedCrossRef

Ka H, Hunt JS (2003) Temporal and spatial patterns of expression of inhibitors of apoptosis in human placentas. Am J Pathol 163:413–422PubMed

Posl M, Amling M, Werner M et al (1994) Osteosarcoma—apoptosis and proliferation. Study of Bcl-2 expression. Pathologe 15:337–344PubMedCrossRef

Ferrari S, Bertoni F, Zanella L et al (2004) Evaluation of P-glycoprotein, HER-2/ErbB-2, p53, and Bcl-2 in primary tumor and metachronous lung metastases in patients with high-grade osteosarcoma. Cancer 100:1936–1942PubMedCrossRef

Title: Livin and Bcl-2 expression in high-grade osteosarcoma
Authors: T. Nedelcu
B. Kubista
A. Koller
I. Sulzbacher
I. Mosberger
F. Arrich
K. Trieb
R. Kotz
C. D. Toma
Publication date: 01-02-2008
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 2/2008
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-007-0276-z

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Abstract

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