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Plasma MMP-2-TIMP-2 complex levels measured during follow-up predict a risk of relapse in patients with malignant lymphoma

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Abstract Objectives: 

Circulating gelatinases and their tissue inhibitors measured at diagnosis have been shown to exhibit prognostic relevance in several solid tumours. The clinical data concerning their role in follow-up of cancer are still very preliminary. The aim of this study was to find out whether the concentrations of these circulating markers could be used as follow-up markers predicting the risk of lymphoma relapse. Methods: 

Here, we investigated these circulating molecules in a large (n = 126) follow-up material of lymphoma patients and in healthy controls (n = 44). The plasma samples of patients with Hodgkin’s lymphoma (n = 31), non-Hodgkin’s lymphoma (n = 95), and healthy controls were analysed by enzyme-linked immunosorbent assay for matrix metalloproteinase-9 (MMP-9), proMMP-2, matrix metalloproteinase-2-tissue inhibitor of metalloproteinase-2 (MMP-2-TIMP-2) complex, TIMP-1, and TIMP-2. Results: 

The patients with the highest plasma levels of MMP-2-TIMP-2 complex had a 3-fold risk of relapse when compared to the patients with lower levels (P = 0.036). Plasma levels of proMMP-2 and MMP-2-TIMP-2 complex as well as the proMMP-2/TIMP-2 ratio were significantly higher in patients with active lymphoma and those in remission when compared to healthy controls. On the contrary, the values of TIMP-2 were significantly lower in lymphoma patients than in controls. Conclusions: 

This study shows that lymphoma patients with the highest levels of MMP-2-TIMP-2 complex are at a marked risk of relapse. Moreover, plasma levels of MMP-2-TIMP-2 complex, proMMP-2, TIMP-2, and proMMP-2/TIMP-2 ratio are at abnormal level in patients with newly diagnosed lymphoma and those in remission when compared to healthy controls. They remain abnormal even after successful lymphoma treatments.
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Keywords: follow-up; gelatinase; lymphoma; matrix metalloproteinase-2; matrix metalloproteinase-2-tissue inhibitor of metalloproteinase-2 complex; matrix metalloproteinase-9; plasma marker; relapse risk; tissue inhibitor of metalloproteinase-1; tissue inhibitor of metalloproteinase-2

Document Type: Research Article

Publication date: January 1, 2008

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