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Prognostic significance of 18F-FDG uptake in primary osteosarcoma after but not before chemotherapy: a possible association with autocrine motility factor/phosphoglucose isomerase expression

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Abstract

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma (OS). 18-F-fluorodeoxy-d-glucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that correlates with histological grading in musculoskeletal sarcomas. To determine the prognostic value of FDG PET in patients receiving chemotherapy, 13 patients were evaluated by FDG-PET, and followed for more than 4 years. FDG PET standardized uptake values before (SUV1) and after (SUV2) chemotherapy were analyzed and correlated with the expression of metastasis-related glycolytic enzyme, autocrine motility factor (AMF)/phosphoglucose isomerase (PGI) by immunohistochemical examination in surgically excised tumors. Although mean SUV1 for OS patients with metastatic lesions were similar to those in the completely disease-free (CDF) group (6.5 vs. 6.6, respectively, P = 0.975), mean SUV2 for OS with metastatic lesions were significantly higher than those in the CDF group (5.1 vs. 2.5, respectively, P = 0.0445). Interestingly, immunohistochemical analysis using anti-AMF/PGI antibody revealed that SUV2 correlated significantly with the AMF/PGI staining titers (P = 0.0303), while no correlation between SUV1 and the AMF/PGI staining titers existed (P = 0.964). The present study suggests that FDG PET after chemotherapy may provide information for AMF/PGI-related metastatic potentiality of residual tumors located out side of the area surgically resected afterward, and then lead to a useful prediction of the patients’ prognosis.

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Abbreviations

AMF:

Autocrine motility factor

DOD:

Death of disease

FDG:

18-F-Fluorodeoxy-d-glucose

IHC:

Immunohistochemistry

NED:

No evidence of disease

OS:

Osteosarcoma

PET:

Positron emission tomography

PGI:

Phosphoglucose isomerase

PHI:

Phosphohexose isomerase

ROI:

Region of interest

SUV:

Standardized uptake value

References

  1. 1.

    Link MP, Goorin AM, Miser AW et al (1986) The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 314:1600

  2. 2.

    Bruland OS, Pihl A (1997) On the current management of osteosarcoma: a critical evaluation and a proposal for a modified treatment strategy. Eur J Cancer 33:1725–1731

  3. 3.

    Davis AM, Bell RS, Goodwin PJ (1994) Prognostic factors in osteosarcoma: a critical review. J Clin Oncol 12:423–431

  4. 4.

    Windhager R, Millesi H, Kotz R (1995) Resection-replatation for primary malignant tumours of the arm: an alternative to fore-quarter amputation. J Bone Joint Surg Br 77:176–184

  5. 5.

    Watanabe H, Ahmed AR, Shinozaki T et al (2003) Reconstruction with autologous pasteurized whole knee joint: part 2, application for osteosarcoma of the proximal tibia. J Orthop Sci 8:180–186

  6. 6.

    Bielack SS, Kempf-Bielack B, Delling G et al (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 20:776–790

  7. 7.

    Lewis IJ, Nooij MA, Whelan J et al (2007) Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst 99:112–128

  8. 8.

    Saeter G, Hoie J, Stenwig AE et al (1995) Systemic relapse of patients with osteogenic sarcoma: prognostic factors for long term survival. Cancer 75:1084–1093

  9. 9.

    Fletcher BD (1997) Imaging pediatric bone sarcomas: diagnosis and treatment-related issues. Radiol Clin North Am 35:1477–1494

  10. 10.

    Lawrence JA, Babyn PS, Chan HS et al (1993) Extremity osteosarcoma in childhood: prognostic value of radiologic imaging. Radiology 189:43–47

  11. 11.

    Rozental JM, Levine RL, Nicles RJ (1991) Changes in glucose uptake by malignant glicomas: preliminary study of prognostic significance. J Neurooncol 10:75–83

  12. 12.

    Kern KA, Brunetti A, Norton JA et al (1988) Metabolic imaging of human extremity musculoskeletal tumors by PET. J Nucl Med 29:181–186

  13. 13.

    Brenner W, Bohuslavizki KH, Eary JF et al (2003) PET imaging of osteosarcoma. J Nucl Med 44:930–942

  14. 14.

    Eary JF, O`Sullivan F, Powitan Y et al (2002) Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective analysis. Eur J Nucl Med 29:1149–1154

  15. 15.

    Adler LP, Blair HF, Makley JT et al (1991) Noninvasive grading of musculoskeletal tumors using PET. J Nucl Med 32:1508–1512

  16. 16.

    Nieweg OE, Pruim J, Van Genkel RJ et al (1996) Fluorine-18-fluorodeoxyglucose PET imaging of soft-tissue sarcoma. J Nucl Med 37:257–261

  17. 17.

    Watanabe H, Inoue T, Shinozaki T et al (2000) PET imaging of musculoskeletal tumors with F-18 alpha-methyltyrosine: comparison with F-18 fluorodeoxyglucose PET. Eur J Nucl Med 27:1509–1517

  18. 18.

    Griffeth LK, Dehdashti F, McGuire AH et al (1992) PET evaluation of soft-tissue masses with fluorine-18 fluoro-2-deoxy-d-glucose. Radiology 182:185–194

  19. 19.

    Suzuki H, Watanabe H, Shinozaki T et al (2004) PET imaging of musculoskeletal tumors in the shoulder girdle. J Shoulder Elbow Surg 13:635–647

  20. 20.

    Watanabe H, Shinozaki T, Yanagawa T et al (2000) Glucose metabolic analysis of musculoskeletal tumours using 18fluorine-FDG PET as an aid to preoperative planning. J Bone Joint Surg Br 82:760–767

  21. 21.

    Folpe AL, Lyles RH, Sprouse JT et al (2000) (F-18) fluorodeoxy-glucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 6:1279–1287

  22. 22.

    Messa C, Landone C, Pozzato C et al (2000) Is there a role for FDG PET in the diagnosis of musculoskeletal neoplasms [commentary]? J Nucl Med 41:1702–1703

  23. 23.

    Hawkins DS, Rajendran JG, Conrad EU III et al (2002) Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-d-glucose positron emission tomography. Cancer 94:3277–3284

  24. 24.

    Schulte M, Brecht-Krauss D, Werner M et al (1999) Evaluation of neoadjuvant chemotherapy response of osteogenic sarcoma using FDG-PET. J Nucl Med 40:1637–1643

  25. 25.

    Franzius C, Bielack S, Flege S et al (2002) Prognostic significance of 18F-FDG and 99mTc-methylene diphosphonate uptake in primary osteosarcoma. J Nucl Med 43:1012–1017

  26. 26.

    Liotta LA, Mandler R, Murano G et al (1986) Tumor cell autocrine motility factor. Proc Natl Acad Sci USA 83:3302–3306

  27. 27.

    Watanabe H, Carmi P, Hogan V et al (1991) Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. J Biol Chem 266:13442–13448

  28. 28.

    Gurney ME, Apatoff BR, Spear GT et al (1986) Neuroleukin: a lymphokine product of lectin stimulated T cells. Science 234:574–581

  29. 29.

    Luo Y, Long JM, Lu C et al (2002) A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78. J Neurochem 80:354–361

  30. 30.

    Xu W, Seiter K, Feldman E et al (1996) The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase. Blood 87:4502–4506

  31. 31.

    Zhi J, Sommerfeldt DW, Rubin CT et al (2001) Differential expression of neuroleukin in osseous tissues and its involvement in mineralization during osteoblast differentiation. J Bone Miner Res 16:1994–2004

  32. 32.

    Watababe H, Takehara K, Date M et al (1996) Tumor cell autocrine motility factor is neuroleukin/phosphohexose isomerase polypeptide. Cancer Res 56:2960–2963

  33. 33.

    Takanami I, Takeuchi K, Naruke M et al (1998) Autocrine motility factor in pulmonary adenocarcinomas: results of an immunohistochemical study. Tumour Biol 19:384–389

  34. 34.

    Dobashi Y, Watanabe H, Matsubara M et al (2006) Autocrine motility factor/glucose-6-phosphate isomerase is a possible predictor of metastasis in bone and soft tissue tumours. J Pathol 208:44–53

  35. 35.

    Dobashi Y, Watanabe H, Hirashima S et al (2006) Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas. J Pathol 210:431–440

  36. 36.

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

  37. 37.

    Shinozaki T, Watanabe H, Yanagawa T et al (2002) Pirarubicin-based versus doxorubicin-based osteosarcoma chemotherapy. Ann Pharmacother 36:996–999

  38. 38.

    Shinozaki T, Watanabe H, Tomidokoro R et al (2000) Successful rescue by oral cholestyramine of a patient with methotrexate nephrotoxity: nonrenal excretion of serum methotrexate. Med Pediatr Oncol 34:226–228

  39. 39.

    Kawaguchi N, Matumoto S, Manabe J (1995) New method of evaluating the surgical margin and safety margin for musculoskeletal sarcoma, analyzed on the basis of 457 surgical cases. J Cancer Res Clin Oncol 121:555–563

  40. 40.

    Hawkins DS, Schuetze SM, Butrynski JE et al (2005) [18F]fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors. J Clin Oncol 23:8828–8834

  41. 41.

    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

  42. 42.

    Mantel M (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170

  43. 43.

    Franzius C, Daldrup-Link HE et al (2001) FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: comparison with spiral CT. Ann Oncol 12:479–486

  44. 44.

    Franzius C, Sciuk J, Brinkschmidt C et al (2000) Evaluation of chemotherapy response in primary bone tumors with F-18 FDG positron emission tomography compared with histologically assessed tumor necrosis. Clin Nucl Med 25:874–881

  45. 45.

    Reske SN, Grillenberger KG, Glatting G et al (1997) Overexpression of glucose transporter 1 and increased FDG uptake in pancreatic carcinoma. J Nucl Med 38:1344–1348

  46. 46.

    Niizeki H, Kobayashi M, Horiuchi I, Hosokawa M, et al (2002) Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells. Br J Cancer 86:1914–1919

  47. 47.

    Yanagawa T, Watanabe H, Takeuchi T et al (2004) Overexpression of autocrine motility factor in metastatic tumor cells: possible association with augmented expression of KIF3A and GDI-beta. Lab Invest 84:513–522

  48. 48.

    Watanabe H, Kanbe K, Chigira M (1994) Differential purification of autocrine motility factors derived from a murine protein-free fibrosarcoma. Clin Exp Metastat 12:155–163

  49. 49.

    Schwartz MK (1976) Laboratory aids to diagnosis: enzymes. Cancer 37:542–548

  50. 50.

    Tsutsumi S, Hogan V, Nabi IR et al (2003) Overexpression of the autocrine motility factor/phosphoglucose isomerase induces transformation and survival of NIH-3T3 fibroblast. Cancer Res 63:242–249

  51. 51.

    Yanagawa T, Funasaka T, Tsutsumi S et al (2004) Novel roles of the autocrine motility factor/phophoglucose isomerase in tumor malignancy. Endocr Relat Cancer 11:749–759

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Acknowledgement

This work was supported in part by a Grant-in-Aid for scientific research (C) 16591472 (H.W.) from the Japan Society for the Promotion of Science.

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Correspondence to Hideomi Watanabe.

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Sato, J., Yanagawa, T., Dobashi, Y. et al. Prognostic significance of 18F-FDG uptake in primary osteosarcoma after but not before chemotherapy: a possible association with autocrine motility factor/phosphoglucose isomerase expression. Clin Exp Metastasis 25, 427–435 (2008) doi:10.1007/s10585-008-9147-5

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Keywords

  • Autocrine motility factor
  • Chemotherapy
  • FDG PET
  • Glycolysis
  • Hypoxia
  • Osteosarcoma
  • Metastasis
  • Phosphoglucose isomerase