Skip to main content

Advertisement

SpringerLink
Log in

Longitudinal prospective study of matrix metalloproteinase-9 as a serum marker in gliomas

  • Clinical Study – Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The objective of this study was to evaluate if longitudinal measurements of serum matrix metalloproteinase-9 (MMP-9) correlated with disease status or survival in adults with gliomas. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. MMP-9 levels were determined by ELISA and correlated with radiographic disease status and survival. Forty-one patients with low-grade gliomas, 105 with anaplastic gliomas, and 197 with glioblastoma enrolled in this study from August 2002 to September 2008. A total of 1,684 serum samples (97.1% of all MMP-9 samples) had a matching MRI scan. No statistically significant association was observed between levels of serum MMP-9 and radiographic disease status in low-grade gliomas (P = 0.98), anaplastic gliomas (P = 0.39) or glioblastomas (P = 0.33). Among patients with glioblastoma, longitudinal increases in MMP-9 had a weak association with shorter survival (HR = 1.1 per each doubling in MMP-9 levels, 95% CI, 1.0–1.3, P = 0.04) but they were not independently associated with survival when adjusted for age, extent of resection, and performance status. Changes in serum MMP-9 were not associated with survival in the anaplastic glioma cohort. Serum MMP-9 showed no utility in determining glioma disease status and was not a clinically relevant prognostic marker of survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. van den Bent MJ, Vogelbaum MA, Wen PY, Macdonald DR, Chang SM (2009) End point assessment in gliomas: novel treatments limit usefulness of classical Macdonald’s Criteria. J Clin Oncol 27:2905–2908. doi:10.1200/JCO.2009.22.4998

    Article  PubMed  Google Scholar 

  2. Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 24:2707–2714. doi:10.1200/JCO.2005.04.3414

    Article  PubMed  CAS  Google Scholar 

  3. van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24:2715–2722. doi:10.1200/JCO.2005.04.6078

    Article  PubMed  Google Scholar 

  4. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003. doi:10.1056/NEJMoa043331

    Article  PubMed  CAS  Google Scholar 

  5. Lakka SS, Rajan M, Gondi C, Yanamandra N, Chandrasekar N, Jasti SL, Adachi Y, Siddique K, Gujrati M, Olivero W, Dinh DH, Kouraklis G, Kyritsis AP, Rao JS (2002) Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene 21:8011–8019. doi:10.1038/sj.onc.1205894

    Article  PubMed  CAS  Google Scholar 

  6. Rao JS, Yamamoto M, Mohaman S, Gokaslan ZL, Fuller GN, Stetler-Stevenson WG, Rao VH, Liotta LA, Nicolson GL, Sawaya RE (1996) Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in human gliomas. Clin Exp Metastasis 14:12–18

    Article  PubMed  CAS  Google Scholar 

  7. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744. doi:10.1038/35036374

    Article  PubMed  CAS  Google Scholar 

  8. Hormigo A, Gu B, Karimi S, Riedel E, Panageas KS, Edgar MA, Tanwar MK, Rao JS, Fleisher M, DeAngelis LM, Holland EC (2006) YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin Cancer Res 12:5698–5704. doi:10.1158/1078-0432.CCR-06-0181

    Article  PubMed  CAS  Google Scholar 

  9. Clarke JL, Iwamoto FM, Sul J, Panageas K, Lassman AB, DeAngelis LM, Hormigo A, Nolan CP, Gavrilovic I, Karimi S, Abrey LE (2009) Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J Clin Oncol 27:3861–3867. doi:10.1200/JCO.2008.20.7944

    Article  PubMed  CAS  Google Scholar 

  10. Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

    PubMed  CAS  Google Scholar 

  11. Zeger SL, Liang KY (1992) An overview of methods for the analysis of longitudinal data. Stat Med 11:1825–1839

    Article  PubMed  CAS  Google Scholar 

  12. Cox D, Oakes D (1990) Analysis of survival data. Chapman & Hill, New York

    Google Scholar 

  13. Komatsu K, Nakanishi Y, Nemoto N, Hori T, Sawada T, Kobayashi M (2004) Expression and quantitative analysis of matrix metalloproteinase-2 and -9 in human gliomas. Brain Tumor Pathol 21:105–112

    Article  PubMed  CAS  Google Scholar 

  14. Tutton MG, George ML, Eccles SA, Burton S, Swift RI, Abulafi AM (2003) Use of plasma MMP-2 and MMP-9 levels as a surrogate for tumour expression in colorectal cancer patients. Int J Cancer 107:541–550. doi:10.1002/ijc.11436

    Article  PubMed  CAS  Google Scholar 

  15. Ranuncolo SM, Matos E, Loria D, Vilensky M, Rojo R, Bal de Kier Joffe E, Ines Puricelli L (2002) Circulating 92-kilodalton matrix metalloproteinase (MMP-9) activity is enhanced in the euglobulin plasma fraction of head and neck squamous cell carcinoma. Cancer 94:1483–1491. doi:10.1002/cncr.10356

    Article  PubMed  CAS  Google Scholar 

  16. Zucker S, Cao J (2005) Measurement of matrix metalloproteinases in serum of patients with melanoma: snarled in technical pitfalls. Clin Cancer Res 11:5069–5070. doi:10.1158/1078-0432.CCR-05-0774

    Article  PubMed  CAS  Google Scholar 

  17. Nikkola J, Vihinen P, Vuoristo MS, Kellokumpu-Lehtinen P, Kahari VM, Pyrhonen S (2005) High serum levels of matrix metalloproteinase-9 and matrix metalloproteinase-1 are associated with rapid progression in patients with metastatic melanoma. Clin Cancer Res 11:5158–5166. doi:10.1158/1078-0432.CCR-04-2478

    Article  PubMed  CAS  Google Scholar 

  18. Ranuncolo SM, Armanasco E, Cresta C, Bal De Kier Joffe E, Puricelli L (2003) Plasma MMP-9 (92 kDa-MMP) activity is useful in the follow-up and in the assessment of prognosis in breast cancer patients. Int J Cancer 106:745–751. doi:10.1002/ijc.11288

    Article  PubMed  CAS  Google Scholar 

  19. Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 27:5287–5297. doi:10.1200/JCO.2009.23.5556

    Article  PubMed  CAS  Google Scholar 

  20. Smith ER, Zurakowski D, Saad A, Scott RM, Moses MA (2008) Urinary biomarkers predict brain tumor presence and response to therapy. Clin Cancer Res 14:2378–2386. doi:10.1158/1078-0432.CCR-07-1253

    Article  PubMed  CAS  Google Scholar 

  21. Choe G, Park JK, Jouben-Steele L, Kremen TJ, Liau LM, Vinters HV, Cloughesy TF, Mischel PS (2002) Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype. Clin Cancer Res 8:2894–2901

    PubMed  CAS  Google Scholar 

  22. Gerlach RF, Uzuelli JA, Souza-Tarla CD, Tanus-Santos JE (2005) Effect of anticoagulants on the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities. Anal Biochem 344:147–149. doi:10.1016/j.ab.2005.04.038

    Article  PubMed  CAS  Google Scholar 

  23. Jung K, Lein M, Laube C, Lichtinghagen R (2001) Blood specimen collection methods influence the concentration and the diagnostic validity of matrix metalloproteinase 9 in blood. Clin Chim Acta 314:241–244.

    Article  PubMed  CAS  Google Scholar 

  24. Souza-Tarla CD, Uzuelli JA, Machado AA, Gerlach RF, Tanus-Santos JE (2005) Methodological issues affecting the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activities. Clin Biochem 38:410–414. doi:10.1016/j.clinbiochem.2005.02.010

    Article  PubMed  CAS  Google Scholar 

  25. Rouy D, Ernens I, Jeanty C, Wagner DR (2005) Plasma storage at −80 degrees C does not protect matrix metalloproteinase-9 from degradation. Anal Biochem 338:294–298. doi:10.1016/j.ab.2004.10.052

    Article  PubMed  CAS  Google Scholar 

  26. Friedberg MH, Glantz MJ, Klempner MS, Cole BF, Perides G (1998) Specific matrix metalloproteinase profiles in the cerebrospinal fluid correlated with the presence of malignant astrocytomas, brain metastases, and carcinomatous meningitis. Cancer 82:923–930

    Article  PubMed  CAS  Google Scholar 

  27. Groves MD, Puduvalli VK, Hess KR, Jaeckle KA, Peterson P, Yung WK, Levin VA (2002) Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. J Clin Oncol 20:1383–1388

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Grant support to Adília Hormigo from the Society for Memorial Sloan-Kettering Cancer Center.

Conflict of interests

None.

Author information

Author notes

  1. Fabio M. Iwamoto

    Present address: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

  2. Andreas F. Hottinger

    Present address: Department of Oncology, Geneva University Hospital, Geneva, Switzerland

Authors and Affiliations

  1. The Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Fabio M. Iwamoto, Andreas F. Hottinger, Sasan Karimi, Andrew B. Lassman, Lauren E. Abrey, Lisa M. DeAngelis, Eric C. Holland & Adília Hormigo

  2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Fabio M. Iwamoto, Andreas F. Hottinger, Jocelynn Dantis, Maryam Jahdi, Andrew B. Lassman, Lauren E. Abrey, Lisa M. DeAngelis, Eric C. Holland & Adília Hormigo

  3. Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Sasan Karimi

  4. Department of Epidemiology-Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Elyn Riedel & Katherine S. Panageas

  5. Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Martin Fleisher

  6. Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Eric C. Holland

  7. Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Eric C. Holland

Authors
  1. Fabio M. Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas F. Hottinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sasan Karimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elyn Riedel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jocelynn Dantis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maryam Jahdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Katherine S. Panageas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrew B. Lassman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lauren E. Abrey
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Martin Fleisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lisa M. DeAngelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Eric C. Holland
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Adília Hormigo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adília Hormigo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwamoto, F.M., Hottinger, A.F., Karimi, S. et al. Longitudinal prospective study of matrix metalloproteinase-9 as a serum marker in gliomas. J Neurooncol 105, 607–612 (2011). https://doi.org/10.1007/s11060-011-0628-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0628-z

Keywords

Search

Navigation