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Expression of the matrix metalloproteinase 9 in Hodgkin's disease is independent of EBV status
  1. J R Flavell1,
  2. K R N Baumforth1,
  3. D M Williams2,
  4. M Lukesova3,
  5. J Madarova3,
  6. V Noskova3,
  7. J Prochazkova3,
  8. D Lowe1,
  9. Z Kolar3,
  10. P G Murray1,
  11. P N Nelson1
  1. 1Biomedical Science Research Laboratories, School of Health Sciences, University of Wolverhampton, Wolverhampton WV1 1DJ, UK
  2. 2CRC Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TJ, UK
  3. 3Institute of Pathology, Faculty of Medicine, and Laboratory of Molecular Pathology, Centre of Molecular Biology and Medicine (CMBM), Palacky University, Olomouc, CZ-77515, Czech Republic
  1. Dr Nelson email: P.N.NELSON{at}


Background—In vitro the Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP-1) has been shown to upregulate expression of matrix metalloproteinase 9 (MMP-9), a member of a family of zinc dependent endopeptidases that is believed to facilitate tumour invasion and metastasis by degradation of the extracellular matrix.

Aim—To test whether the expression of MMP-9 in Hodgkin's disease correlates with EBV status and survival and to investigate whether LMP-1 expression affects MMP-9 concentrations in the Hodgkin's disease cell line, L428.

Methods—MMP-9 expression was measured by means of immunohistochemistry in a series of Hodgkin's disease tumours and this expression was correlated with EBV status and survival. The influence of LMP-1 on MMP-9 expression was also investigated in the Hodgkin's disease cell line, L428.

Results—MMP-9 expression was demonstrated in the malignant Hodgkin and Reed-Sternberg cells of all (n = 86) formalin fixed, paraffin wax embedded Hodgkin's disease tumours examined. Although the intensity of MMP-9 immunostaining varied between cases, there was no correlation between MMP-9 expression and EBV status or survival. MMP-9 expression was also detected in a variety of non-malignant cells, including fibroblasts. MMP-9 was detected by zymography in the L428 and KMH2 Hodgkin's disease cell lines, whereas low or undetectable amounts of MMP-9 were found in the L591 Hodgkin's disease cell line. Induction of LMP-1 expression in the Hodgkin's disease cell line L428 did not result in a detectable increase in the values of MMP-9 as measured by zymography.

Conclusions—These results demonstrate that MMP-9 is consistently expressed by the Hodgkin and Reed-Sternberg cells of Hodgkin's disease tumours and by the Hodgkin's disease cell lines, L428 and KMH2. However, this expression does not appear to be related either to LMP-1 values or to survival.

  • matrix metalloproteinase 9
  • Hodgkin's disease
  • Epstein-Barr virus
  • latent membrane protein 1

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