title: Plasma MMP-2-TIMP-2 complex levels measured during follow-up predict a risk of relapse in patients with malignant lymphoma.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland. heli@kyllonen.fi
authors.forename: Heli
authors.initials: H
authors.lastname: Pennanen
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008223:Lymphoma / Q000175:diagnosis / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000097:blood*; D011237:Predictive Value of Tests; D012008:Recurrence; D012074:Remission Induction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D046912:Multiprotein Complexes; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2