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

Abstract

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. 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. 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. 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.