Abstract
Traditional prognostic determinants in osteosarcoma have included demographics (age, sex), tumour size, site, stage, and the response to chemotherapy. Many of these are determined using varying techniques and units of measurement, which can make comparison between studies difficult. The absence of survival difference between limb sparing surgery and amputation has been repeatedly demonstrated in primary disease, and even in the setting of pathological fracture. On the other hand, there is still some controversy over the existence of increased local recurrence for limb-sparing surgery, and the implications of this. Commonly used prognostic determinants such as metastases, and response to chemotherapy enable a high degree of prognostic accuracy but usually at a late stage in the course of disease. Leading on from this, there is a need to uncover molecular pathways with specific influence over osteosarcoma progression to facilitate earlier treatment changes. Some important pathways are already being defined, for example the association of CXCR4 with metastases on presentation, the likelihood of doxorubicin resistance with positive P-glycoprotein, and the reduced survival prediction of over expressed survivin. It is anticipated that the future of osteosarcoma treatment will involve treatment tailored to the molecular profile of tumours at diagnosis, adjuvant therapy directed towards dysfunctional molecular pathways rather than the use of cytotoxics, and a more standardised approach to the measurement of clinical prognostic factors.
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Abbreviations
- VEGF:
-
Vascular endothelial growth factor
- MVD:
-
Microvascular density
- PEDF:
-
Pigment epithelium-derived factor
- MMP:
-
Matrix metalloproteinase
- RECK:
-
Reversion-inducing cyteine rich protein with Kazal motifs
- uPA:
-
Urokinase plasminogen activator
- P-gp:
-
P-glycoprotein
- CXCR:
-
Chemokine receptor
References
Abudu A, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ (1996) The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J Bone Joint Surg Br 78(5):694–698
Aksnes LH, Hall KS, Folleraas G, Stenwig AE, Bjerkehagen B, Taksdal I, Winderen M, Bruland OS, Saeter G (2006) Management of high-grade bone sarcomas over two decades: the Norwegian Radium Hospital experience. Acta Oncol 45(1):38–46
Ambrogi V, Paci M, Pompeo E, Mineo TC (2000) Transxiphoid video-assisted pulmonary metastasectomy: relevance of helical computed tomography occult lesions. Ann Thorac Surg 70(6):1847–1852
Antunes M, Bernardo J, Salete M, Prieto D, Eugénio L, Tavares P (1999) Excision of pulmonary metastases of osteogenic sarcoma of the limbs. Eur J Cardiothorac Surg 15(5):592–596
Apffelstaedt JP, Driscoll DL, Karakousis CP (1995) Partial and complete internal hemipelvectomy: complications and long-term follow-up. J Am Coll Surg 181(1):43–48
Apffelstaedt JP, Driscoll DL, Spellman JE, Velez AF, Gibbs JF, Karakousis CP (1996) Complications and outcome of external hemipelvectomy in the management of pelvic tumors. Ann Surg Oncol 3(3):304–309
Bacci G, Avella M, Picci P, Dallari D, Malaguti C, Biagini R, Ruggieri P, Balladelli A, Ferrari S, Caldora P (1990) Primary chemotherapy and delayed surgery for malignant fibrous histiocytoma of bone in the extremity. Tumori 76(6):537–542
Bacci G, Donati D, Manfrini M, Forni C, Bertoni F, Gherlinzoni F, Biagini R, Campanacci M (1998) Local recurrence after surgical or surgical-chemotherapeutic treatment of osteosarcoma of the limbs. Incidence, risk factors and prognosis. Minerva Chir 53(7–8):619–629
Bacci G, Ferrari S, Longhi A, Perin S, Forni C, Fabbri N, Salduca N, Versari M, Smith KV (2001) Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer 37(1):32–38
Bacci G, Longhi A, Ferrari S, Lari S, Manfrini M, Donati D, Forni C, Versari M (2002) Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute. Oncol Rep 9(1):171–175
Bacci G, Ferrari S, Longhi A, Donati D, Manfrini M, Giacomini S, Briccoli A, Forni C, Galletti S (2003) Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 74(4):449–454
Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P (2006) Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer 106(5):1154–1161
Baldini N, Scotlandi K, Barbanti-Bròdano G, Manara MC, Maurici D, Bacci G, Bertoni F, Picci P, Sottili S, Campanacci M (1995) Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med 333(21):1380–1385
Baldini N, Scotlandi K, Serra M, Picci P, Bacci G, Sottili S, Campanacci M (1999) P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy. J Orthop Res 17(5):629–632
Beedles KE, Sharpe PT, Wagner EF, Grigoriadis AE (1999) A putative role for c-Fos in the pathophysiology of Paget’s disease. J Bone Miner Res 14(Suppl 2):21–28
Benassi MS, Molendini L, Gamberi G, Ragazzini P, Sollazzo MR, Merli M, Asp J, Magagnoli G, Balladelli A, Bertoni F, Picci P (1999) Alteration of pRb/p16/cdk4 regulation in human osteosarcoma. Int J Cancer 84(5):489–493
Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K (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(3):776–790
Bieling P, Bielack S, Delling G, Jürgens H, Kotz R, Dose C, Astheimer H, Exner G, Gadner H, Graf N (1991) Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study. Klin Padiatr 203(4):220–230
Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K (1996) Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol 14(3):848–858
Bouck N (2002) PEDF: anti-angiogenic guardian of ocular function. Trends Mol Med 8(7):330–334
Briccoli A, Rocca M, Salone M, Bacci G, Ferrari S, Balladelli A, Mercuri M (2005) Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer 104(8):1721–1725
Carsi B, Rock MG (2002) Primary osteosarcoma in adults older than 40 years. Clin Orthop Relat Res 397:53–61
Chan HS, Grogan TM, Haddad G, DeBoer G, Ling V (1997) P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy. J Natl Cancer Inst 89(22):1706–1715
Chandar N, Billig B, McMaster J, Novak J (1992) Inactivation of p53 gene in human and murine osteosarcoma cells. Br J Cancer 65(2):208–214
Chiou SK, Jones MK, Tarnawski AS (2003) Survivin—an anti-apoptosis protein: its biological roles and implications for cancer and beyond. Med Sci Monit 9(4):PI25–PI29
Choong PF, Nadesapillai AP (2003) Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clin Orthop Relat Res 415(Suppl):S46–S58
Choong PF, Fernö M, Akerman M, Willén H, Långström E, Gustafson P, Alvegård T, Rydholm A (1996) Urokinase-plasminogen-activator levels and prognosis in 69 soft-tissue sarcomas. Int J Cancer 69(4):268–272
Daecke W, Bielack S, Martini AK, Ewerbeck V, Jürgens H, Kotz R, Winkelmann W, Kabisch H, Kevric M, Bernd L (2005) Osteosarcoma of the hand and forearm: experience of the Cooperative Osteosarcoma Study Group. Ann Surg Oncol 12(4):322–331
Dass CR, Nadesapillai AP, Robin D, Howard ML, Fisher JL, Zhou H, Choong PF (2005) Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma. Clin Exp Metastasis 22(8):643–652
Davis AM, Bell RS, Goodwin PJ (1994) Prognostic factors in osteosarcoma: a critical review. J Clin Oncol 12(2):423–431
Davis AM, Devlin M, Griffin AM, Wunder JS, Bell RS (1999) Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: a matched case-control study. Arch Phys Med Rehabil 80(6):615–618
Daw NC, Billups CA, Rodriguez-Galindo C, McCarville MB, Rao BN, Cain AM, Jenkins JJ, Neel MD, Meyer WH (2006) Metastatic osteosarcoma. Cancer 106(2):403–412
Dutour A, Monteil J, Paraf F, Charissoux JL, Kaletta C, Sauer B, Naujoks K, Rigaud M (2005) Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor. Mol Ther 11(2):311–319
Eckardt JJ, Eilber FR, Dorey FJ, Mirra JM (1985) The UCLA experience in limb salvage surgery for malignant tumors. Orthopedics 8(5):612–621
Ek ET, Dass CR, Choong PF (2006a) Pigment epithelium-derived factor: a multimodal tumor inhibitor. Mol Cancer Ther 5(7):1641–1646
Ek ET, Ojaimi J, Kitagawa Y, Choong PF (2006b) Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma? Oncol Rep 16(1):17–23
Ek ET, Dass CR, Contreras KG, Choong PF (2007a) Inhibition of orthotopic osteosarcoma growth and metastasis by multitargeted antitumor activities of pigment epithelium-derived factor. Clin Exp Metastasis 24(2):93–106
Ek ET, Dass CR, Contreras KG, Choong PF (2007b) Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis. Cancer Gene Ther 14(7):616–626
Enneking WF, Spanier SS, Goodman MA (1980) A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res 153:106–120
Ferrari S, Bertoni F, Zanella L, Setola E, Bacchini P, Alberghini M, Versari M, Bacci G (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(9):1936–1942
Feugeas O, Guriec N, Babin-Boilletot A, Marcellin L, Simon P, Babin S, Thyss A, Hofman P, Terrier P, Kalifa C, Brunat-Mentigny M, Patricot LM, Oberling F (1996) Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma. J Clin Oncol 14(2):467–472
Finlay CA, Hinds PW, Tan TH, Eliyahu D, Oren M, Levine AJ (1988) Activating mutations for transformation by p53 produce a gene product that forms an hsc70–p53 complex with an altered half-life. Mol Cell Biol 8(2):531–539
Folkman J (1982) Angiogenesis: initiation and control. Ann N Y Acad Sci 401:212–227
Folkman J (2004) Endogenous angiogenesis inhibitors. APMIS 112(7–8):496–507
Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288(5791):551–556
Foukas AF, Deshmukh NS, Grimer RJ, Mangham DC, Mangos EG, Taylor S (2002) Stage-IIB osteosarcomas around the knee. A study of MMP-9 in surviving tumour cells. J Bone Joint Surg Br 84(5):706–711
Franchi A, Calzolari A, Zampi G (1998) Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumours of the skeleton. Virchows Arch 432(6):515–519
Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, Sollazzo MR, Pompetti F, Merli M, Magagnoli G, Balladelli A, Picci P (1998) C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology 55(6):556–563
Ganesh S, Sier CF, Heerding MM, Griffioen G, Lamers CB, Verspaget HW (1994) Urokinase receptor and colorectal cancer survival. Lancet 344(8919):401–402
Greene FL, Page DL, Fleming ID et al (eds) (2002) AJCC cancer staging manual, 6th edn. Springer, New York
Grimer RJ, Taminiau AM, Cannon SR (2002) Surgical outcomes in osteosarcoma. J Bone Joint Surg Br 84(3):395–400
Grimer RJ, Sommerville S, Warnock D, Carter S, Tillman R, Abudu A, Spooner D (2005) Management and outcome after local recurrence of osteosarcoma. Eur J Cancer 41(4):578–583
Hara H, Akisue T, Fujimoto T, Imabori M, Kawamoto T, Kuroda R, Fujioka H, Yamamoto T, Doita M, Kurosaka M (2006) Expression of VEGF and its receptors and angiogenesis in bone and soft tissue tumors. Anticancer Res 26(6B):4307–4311
Hauben EI, Weeden S, Pringle J, Van Marck EA, Hogendoorn PC (2002) Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer 38(9):1218–1225
Heinsohn S, Evermann U, Zur Stadt U, Bielack S, Kabisch H (2007) Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. Int J Oncol 30(5):1205–1214
Henderson MA, Danks JA, Slavin JL, Byrnes GB, Choong PF, Spillane JB, Hopper JL, Martin TJ (2006) Parathyroid hormone-related protein localization in breast cancers predict improved prognosis. Cancer Res 66(4):2250–2256
Himelstein BP, Asada N, Carlton MR, Collins MH (1998) Matrix metalloproteinase-9 (MMP-9) expression in childhood osseous osteosarcoma. Med Pediatr Oncol 31(6):471–474
Hofmann R, Lehmer A, Buresch M, Hartung R, Ulm K (1996) Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer 78(3):487–492
Holekamp NM, Bouck N, Volpert O (2002) Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration. Am J Ophthalmol 134(2):220–227
Hunter KW (2004) Ezrin, a key component in tumor metastasis. Trends Mol Med 10(5):201–204
Iida K, Nobori T, Matsumine A, Isaka A, Seto M, Shiraishi T, Uchida A (2003) Effect of retinoblastoma tumor suppressor gene expression on chemosensitivity of human osteosarcoma cell lines. Oncol Rep 10(6):1961–1965
Jeon DG, Lee SY, Cho WH, Song WS, Park JH (2006) Primary osteosarcoma in patients older than 40 years of age. J Korean Med Sci 21(4):715–718
Kandioler D, Krömer E, Tüchler H, End A, Müller MR, Wolner E, Eckersberger F (1998) Long-term results after repeated surgical removal of pulmonary metastases. Ann Thorac Surg 65(4):909–912
Kang HG, Kim HS, Kim KJ, Oh JH, Lee MR, Seol SM, Han I (2007) RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness. J Orthop Res 25:696–702
Kawai A, Healey JH, Boland PJ, Lin PP, Huvos AG, Meyers PA (1998a) Prognostic factors for patients with sarcomas of the pelvic bones. Cancer 82(5):851–859
Kawai A, Huvos AG, Meyers PA, Healey JH (1998b) Osteosarcoma of the pelvis. Oncologic results of 40 patients. Clin Orthop Relat Res 348:196–207
Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S (2000) Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 6(2):572–577
Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, Yeung C, Gorlick R, Hewitt SM, Helman LJ (2004) The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med 10(2):182–186
Kido A, Tsutsumi M, Iki K, Takahama M, Tsujiuchi T, Morishita T, Tamai S, Konishi Y (1999) Overexpression of matrix metalloproteinase (MMP)-9 correlates with metastatic potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide (4-HAQO)-induced transplantable osteosarcomas in rats. Cancer Lett 137(2):209–216
Kreuter M, Bieker R, Bielack SS, Auras T, Buerger H, Gosheger G, Jurgens H, Berdel WE, Mesters RM (2004) Prognostic relevance of increased angiogenesis in osteosarcoma. Clin Cancer Res 10(24):8531–8537
Ku JH, Kwak C, Lee HS, Park HK, Lee E, Lee SE (2004) Expression of survivin, a novel inhibitor of apoptosis, in superficial transitional cell carcinoma of the bladder. J Urol 171(2 Pt 1):631–635
Kuhn W, Pache L, Schmalfeldt B, Dettmar P, Schmitt M, Jänicke F, Graeff H (1994) Urokinase (uPA) and PAI-1 predict survival in advanced ovarian cancer patients (FIGO III) after radical surgery and platinum-based chemotherapy. Gynecol Oncol 55(3 Pt 1):401–409
Laverdiere C, Hoang BH, Yang R, Sowers R, Qin J, Meyers PA, Huvos AG, Healey JH, Gorlick R (2005) Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res 11(7):2561–2567
Li YH, Wang C, Meng K, Chen LB, Zhou XJ (2004) Influence of survivin and caspase-3 on cell apoptosis and prognosis in gastric carcinoma. World J Gastroenterol 10(13):1984–1988
Libura J, Drukala J, Majka M, Tomescu O, Navenot JM, Kucia M, Marquez L, Peiper SC, Barr FG, Janowska-Wieczorek A, Ratajczak MZ (2002) CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion. Blood 100(7):2597–2606
Lin A, Rugo HS (2007) The role of trastuzumab in early stage breast cancer: current data and treatment recommendations. Curr Treat Options Oncol 8:47–60
Lindner NJ, Ramm O, Hillmann A, Roedl R, Gosheger G, Brinkschmidt C, Juergens H, Winkelmann W (1999) Limb salvage and outcome of osteosarcoma. The University of Muenster experience. Clin Orthop Relat Res 358:83–89
Lonardo F, Ueda T, Huvos AG, Healey J, Ladanyi M (1997) p53 and MDM2 alterations in osteosarcomas: correlation with clinicopathologic features and proliferative rate. Cancer 79(8):1541–1547
Longhi A, Benassi MS, Molendini L, Macchiagodena M, Picci P, Bacci G (2001) Osteosarcoma in blood relatives. Oncol Rep 8(1):131–136
Malawer MM, Sugarbaker PH (2001) Musculoskeletal cancer surgery—treatment of sarcomas and allied diseases, 2nd edn. Kluwer, The Netherlands, p 609
Mantadakis E, Kim G, Reisch J, McHard K, Maale G, Leavey PJ, Timmons C (2001) Lack of prognostic significance of intratumoral angiogenesis in nonmetastatic osteosarcoma. J Pediatr Hematol Oncol 23(5):286–289
McCabe NP, Angwafo FF III, Zaher A, Selman SH, Kouinche A, Jankun J (2000) Expression of soluble urokinase plasminogen activator receptor may be related to outcome in prostate cancer patients. Oncol Rep 7(4):879–882
McIntyre JF, Smith-Sorensen B, Friend SH, Kassell J, Borresen AL, Yan YX, Russo C, Sato J, Barbier N, Miser J (1994) Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma. J Clin Oncol 12(5):925–930
Mechtersheimer G, Staudter M, Majdic O, Dörken B, Moldenhauer G, Möller P (1990) Expression of HLA-A,B,C, beta 2-microglobulin (beta 2 m), HLA-DR, -DP, -DQ and of HLA-D-associated invariant chain (Ii) in soft-tissue tumors. Int J Cancer 46(5):813–823
Miller CW, Aslo A, Won A, Tan M, Lampkin B, Koeffler HP (1996) Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol 122(9):559–565
Mohammed RA, Green A, El-Shikh S, Paish EC, Ellis IO, Martin SG (2007) Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96(7):1092–1100
Murakami T, Maki W, Cardones AR, Fang H, Tun Kyi A, Nestle FO, Hwang ST (2002) Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Res 62(24):7328–7334
Nathan SS, Gorlick R, Bukata S, Chou A, Morris CD, Boland PJ, Huvos AG, Meyers PA, Healey JH (2006) Treatment algorithm for locally recurrent osteosarcoma based on local disease-free interval and the presence of lung metastasis. Cancer 107(7):1607–1616
Nemunaitis J, Poole C, Primrose J, Rosemurgy A, Malfetano J, Brown P, Berrington A, Cornish A, Lynch K, Rasmussen H, Kerr D, Cox D, Millar A (1998) Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. Clin Cancer Res 4(5):1101–1109
Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, Nishimura S, Imamura Y, Kitayama H, Alexander DB, Ide C, Horan TP, Arakawa T, Yoshida H, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C, Noda M (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107(6):789–800
Onda M, Matsuda S, Higaki S, Iijima T, Fukushima J, Yokokura A, Kojima T, Horiuchi H, Kurokawa T, Yamamoto T (1996) ErbB-2 expression is correlated with poor prognosis for patients with osteosarcoma. Cancer 77(1):71–78
Osaka E, Suzuki T, Osaka S, Yoshida Y, Sugita H, Asami S, Tabata K, Hemmi A, Sugitani M, Nemoto N, Ryu J (2006) Survivin as a prognostic factor for osteosarcoma patients. Acta Histochem Cytochem 39(3):95–100
Ozaki T, Flege S, Liljenqvist U, Hillmann A, Delling G, Salzer-Kuntschik M, Jürgens H, Kotz R, Winkelmann W, Bielack SS (2002) Osteosarcoma of the spine: experience of the Cooperative Osteosarcoma Study Group. Cancer 94(4):1069–1077
Ozaki T, Flege S, Kevric M, Lindner N, Maas R, Delling G, Schwarz R, von Hochstetter AR, Salzer-Kuntschik M, Berdel WE, Jürgens H, Exner GU, Reichardt P, Mayer-Steinacker R, Ewerbeck V, Kotz R, Winkelmann W, Bielack SS (2003) Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group. J Clin Oncol 21(2):334–341
Pakos EE, Ioannidis JP (2003) The association of P-glycoprotein with response to chemotherapy and clinical outcome in patients with osteosarcoma. A meta-analysis. Cancer 98(3):581–589
Paoletti S, Borzi RM, Mazzetti I, Magagnoli G, Macor S, Cattini L, Facchini A (2001) Human osteosarcoma cells release matrix degrading enzymes in response to chemokine activation. Int J Oncol 18(1):11–16
Papachristou DJ, Papavassiliou AG (2007) Osteosarcoma and chondrosarcoma: new signaling pathways as targets for novel therapeutic interventions. Int J Biochem Cell Biol 39(5):857–862
Pardo FS, Lien WW, Fox HS, Efird JT, Aguilera JA, Burton DW, Deftos LJ (2004) Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors. Cancer 101(11):2622–2628
Park YB, Kim HS, Oh JH, Lee SH (2001) The co-expression of p53 protein and P-glycoprotein is correlated to a poor prognosis in osteosarcoma. Int Orthop 24(6):307–310
Park HR, Jung WW, Bacchini P, Bertoni F, Kim YW, Park YK (2006) Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract 202(7):509–515
Parsons AM, Detterbeck FC, Parker LA (2004) Accuracy of helical CT in the detection of pulmonary metastases: is intraoperative palpation still necessary? Ann Thorac Surg 78(6):1910–1916. (discussion 1916–1918)
Pasquini GM, Davey RA, Ho PW, Michelangeli VP, Grill V, Kaczmarczyk SJ, Zajac JD (2002) Local secretion of parathyroid hormone-related protein by an osteoblastic osteosarcoma (UMR 106–01) cell line results in growth inhibition. Bone 31(5):598–605
Perissinotto E, Cavalloni G, Leone F, Fonsato V, Mitola S, Grignani G, Surrenti N, Sangiolo D, Bussolino F, Piacibello W, Aglietta M (2005) Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression. Clin Cancer Res 11(2 Pt 1):490–497
Picci P, Bacci G, Campanacci M, Gasparini M, Pilotti S, Cerasoli S, Bertoni F, Guerra A, Capanna R, Albisinni U (1985) Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy. Regional mapping of viable and nonviable tumor. Cancer 56(7):1515–1521
Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M (1994) Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 12(12):2699–2705
Pillay V, Dass CR, Choong PF (2007) The urokinase plasminogen activator receptor as a gene therapy target for cancer. Trends Biotechnol 25(1):33–39
Pochanugool L, Subhadharaphandou T, Dhanachai M, Hathirat P, Sangthawan D, Pirabul R, Onsanit S, Pornpipatpong N (1997) Prognostic factors among 130 patients with osteosarcoma. Clin Orthop Relat Res 345:206–214
Quan GM, Ojaimi J, Nadesapillai AP, Zhou H, Choong PF (2002) Resistance of epiphyseal cartilage to invasion by osteosarcoma is likely to be due to expression of antiangiogenic factors. Pathobiology 70(6):361–367
Quan GM, Slavin JL, Schlicht SM, Smith PJ, Powell GJ, Choong PF (2005) Osteosarcoma near joints: assessment and implications. J Surg Oncol 91(3):159–166
Rougraff BT, Simon MA, Kneisl JS, Greenberg DB, Mankin HJ (1994) Limb salvage compared with amputation for osteosarcoma of the distal end of the femur. A long-term oncological, functional, and quality-of-life study. J Bone Joint Surg Am 76(5):649–656
Saeki H, Yanoma S, Takemiya S, Sugimasa Y, Akaike M, Yukawa N, Rino Y, Imada T (2007) Antitumor activity of a combination of trastuzumab (Herceptin) and oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2-overexpressing pancreatic cancer. Oncol Rep 18(2):433–439
Sajadi KR, Heck RK, Neel MD, Rao BN, Daw N, Rodriguez-Galindo C, Hoffer FA, Stacy GS, Peabody TD, Simon MA (2004) The incidence and prognosis of osteosarcoma skip metastases. Clin Orthop Relat Res 426:92–96
Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC (2002) Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. J Bone Joint Surg Am 84-A(1):49–57
Shin CY, Lee WJ, Choi JW, Choi MS, Ryu JR, Oh SJ, Cheong JH, Choi EY, Ko KH (2007) Down-regulation of matrix metalloproteinase-9 expression by nitric oxide in lipopolysaccharide-stimulated rat primary astrocytes. Nitric Oxide 16(4):425–432
Shives TC, Dahlin DC, Sim FH, Pritchard DJ, Earle JD (1986) Osteosarcoma of the spine. J Bone Joint Surg Am 68(5):660–668
Simon MA, Aschliman MA, Thomas N, Mankin HJ (1986) Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur. J Bone Joint Surg Am 68(9):1331–1337
Sluga M, Windhager R, Lang S, Heinzl H, Bielack S, Kotz R (1999) Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma. Clin Orthop Relat Res 358:120–127
Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD (2004) CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 64(23):8604–8612
Somers GR, Ho M, Zielenska M, Squire JA, Thorner PS (2005) HER2 amplification and overexpression is not present in pediatric osteosarcoma: a tissue microarray study. Pediatr Dev Pathol 8(5):525–532
Span PN, Sweep CG, Manders P, Beex LV, Leppert D, Lindberg RL (2003) Matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs: a prognostic marker for good clinical outcome in human breast carcinoma. Cancer 97(11):2710–2715
Stempak D, Gammon J, Halton J, Moghrabi A, Koren G, Baruchel S (2006) A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors. J Pediatr Hematol Oncol 28(11):720–728
Szendroi M, Pápai Z, Koós R, Illés T (2000) Limb-saving surgery, survival, and prognostic factors for osteosarcoma: the Hungarian experience. J Surg Oncol 73(2):87–94
Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK (2002) Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res 62(6):1832–1837
Takahashi C, Sheng Z, Horan TP, Kitayama H, Maki M, Hitomi K, Kitaura Y, Takai S, Sasahara RM, Horimoto A, Ikawa Y, Ratzkin BJ, Arakawa T, Noda M (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc Natl Acad Sci USA 95(22):13221–13226
Takenaka K, Ishikawa S, Kawano Y, Yanagihara K, Miyahara R, Otake Y, Morioka Y, Takahashi C, Noda M, Wada H, Tanaka F (2004) Expression of a novel matrix metalloproteinase regulator, RECK, and its clinical significance in resected non-small cell lung cancer. Eur J Cancer 40(10):1617–1623
Takenaka K, Yamagishi S, Jinnouchi Y, Nakamura K, Matsui T, Imaizumi T (2005) Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. Life Sci 77(25):3231–3241
Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC (1998) IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 58(23):5315–5320
Teodoro JG, Evans SK, Green MR (2007) Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. J Mol Med. doi:17589818
Thorpe WP, Reilly JJ, Rosenberg SA (1979) Prognostic significance of alkaline phosphatase measurements in patients with osteogenic sarcoma receiving chemotherapy. Cancer 43(6):2178–2181
Tjin Tham Sjin RM, Naspinski J, Birsner AE, Li C, Chan R, Lo KM, Gillies S, Zurakowski D, Folkman J, Samulski J, Javaherian K (2006) Endostatin therapy reveals a U-shaped curve for antitumor activity. Cancer Gene Ther 13(6):619–627
Tomer G, Cohen IJ, Kidron D, Katz K, Yosipovitch Z, Meller I, Zaizov R (1999) Prognostic factors in non-metastatic limb osteosarcoma: a 20-year experience of one center. Int J Oncol 15(1):179–185
Trieb K, Lehner R, Stulnig T, Sulzbacher I, Shroyer KR (2003) Survivin expression in human osteosarcoma is a marker for survival. Eur J Surg Oncol 29(4):379–382
Truong NU, deB Edwardes MD, Papavasiliou V, Goltzman D, Kremer R (2003) Parathyroid hormone-related peptide and survival of patients with cancer and hypercalcemia. Am J Med 115(2):115–121
Tsukahara T, Kawaguchi S, Torigoe T, Asanuma H, Nakazawa E, Shimozawa K, Nabeta Y, Kimura S, Kaya M, Nagoya S, Wada T, Yamashita T, Sato N (2006) Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8–5. Cancer Sci 97(12):1374–1380
van der Jagt MF, Sweep FC, Waas ET, Hendriks T, Ruers TJ, Merry AH, Wobbes T, Span PN (2006) Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer. Cancer Lett 237(2):289–297
Varmus H (2006) The new era in cancer research. Science 312(5777):1162–1165
Vinodhkumar R, Song YS, Ravikumar V, Ramakrishnan G, Devaki T (2007) Depsipeptide a histone deacetlyase inhibitor down regulates levels of matrix metalloproteinases 2 and 9 mRNA and protein expressions in lung cancer cells (A549). Chem Biol Interact 165(3):220–229
Wadayama B, Toguchida J, Shimizu T, Ishizaki K, Sasaki MS, Kotoura Y, Yamamuro T (1994) Mutation spectrum of the retinoblastoma gene in osteosarcomas. Cancer Res 54(11):3042–3048
Wan X, Mendoza A, Khanna C, Helman LJ (2005) Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res 65(6):2406–2411
Wang W, Luo H, Wang A (2006) Expression of survivin and correlation with PCNA in osteosarcoma. J Surg Oncol 93(7):578–584
Winkler K, Beron G, Kotz R, Salzer-Kuntschik M, Beck J, Beck W, Brandeis W, Ebell W, Erttmann R, Göbel U (1984) Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. J Clin Oncol 2(6):617–624
Wu JX, Carpenter PM, Gresens C, Keh R, Niman H, Morris JW, Mercola D (1990) The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. Oncogene 5(7):989–1000
Yang R, Hoang BH, Kubo T, Kawano H, Chou A, Sowers R, Huvos AG, Meyers PA, Healey JH, Gorlick R (2007) Over-expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma. Int J Cancer 121(5):943–954
Yonemoto T, Tatezaki S, Ishii T, Satoh T, Kimura H, Iwai N (1998) Prognosis of osteosarcoma with pulmonary metastases at initial presentation is not dismal. Clin Orthop Relat Res 349:194–199
Zhou H, Randall RL, Brothman AR, Maxwell T, Coffin CM, Goldsby RE (2003) Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol 25(1):27–32
Acknowledgments
The authors would like to acknowledge the generous support of the Australian Orthopaedic Association, Cancer Council of Victoria, Faculty of Medicine at the University of Melbourne, and The Royal Australasian College of Surgeons.
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Clark, J.C.M., Dass, C.R. & Choong, P.F.M. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol 134, 281–297 (2008). https://doi.org/10.1007/s00432-007-0330-x
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DOI: https://doi.org/10.1007/s00432-007-0330-x