Expression of the matrix metalloproteinase 9 in Hodgkin's disease is independent of EBV status

J R Flavell¹, K R N Baumforth¹, D M Williams², M Lukesova³, J Madarova³, V Noskova³, J Prochazkova³, D Lowe¹, Z Kolar³, P G Murray¹ and P N Nelson¹

¹ Biomedical Science Research Laboratories, School of Health Sciences, University of Wolverhampton, Wolverhampton WV1 1DJ, UK
² CRC Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TJ, UK
³ Institute of Pathology, Faculty of Medicine, and Laboratory of Molecular Pathology, Centre of Molecular Biology and Medicine (CMBM), Palacky University, Olomouc, CZ-77515, Czech Republic

Correspondence to:
Dr Nelson email: P.N.NELSON{at}wlv.ac.uk

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.

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

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