Diverse role of MMP-2 and MMP-9 in the clinicopathological behavior of Hodgkin’s lymphoma Hodgkin’s lymphoma is a malignancy with an excellent prognosis. More than 85% of limited- stage patients are free from disease 10 yr after the treatment (1). However, 45% of stage IV patients still die of this malignancy. The clinical behaviour of the disease, especially in the advanced stage, can be quite variable. There has been intense research activity on the clinical prognostic factors, but there is still a need for biological prognostic and predictive parameters to individually assess each patient’s risk of relapse and to tailor the therapy to maximize the possibilities for long-term disease-free survival while minimizing the risk for long-term side-effects. MMP-2 and MMP-9 (gelatinases A and B) are members of the matrix metalloproteinase family. They are expressed in a wide variety of tissues. They play an integral role in physiologic tissue degradation and remodeling (2). In malignant tumors, expression of both gelatinases is usually linked with invasive behavior (3, 4), growth, and angiogenesis (5). MMP-2 and MMP-9 seem to have prognostic value in several malignant tumors (6–9). Their role in the progression of malignant dis- eases may be much more complicated however, and gelatinases have also complex interactions in inflammation and immunological processes (10). To reach a size of over 1 mm, a tumor needs the capability to induce the host’s endothelial cells to grow into the tumor and to create a new vascular network. This is a multi-step process, involving MMP-2 as one of the key enzymes (11). The extent of new vessel formation is linked to more aggressive disease characteristics in, for example, multiple myeloma and cutaneous T-cell lympho- mas (5, 9). Most of the data concerning gelatinases in malignancies derive from findings on solid tumors and cannot be directly extrapolated to hematolog- ical malignancies, which are biologically divergent from solid tumors. The function of gelatinases in Hodgkin’s disease is not known. The expression of MMP-2 in Hodgkin’s lymphoma has not been previously studied. MMP-9 expression has been seen in malignant Reed–Sternberg cells in Hodgkin’s Kuittinen O, Soini Y, Turpeenniemi-Hujanen T. Diverse role of MMP-2 and MMP-9 in the clinicopathological behavior of Hodgkin’s lymphoma. Eur J Haematol 2002: 69: 205–212. Ó Blackwell Munksgaard 2002. Abstract: This is the first study to describe the role of MMP-2 and MMP-9 in Hodgkin’s disease. Strong MMP-2 expression correlated with a favorable prognosis, while MMP-9 expression showed a tendency toward an adverse outcome. MMP-9 expression correlated with B symptoms and decreased new vessel formation. MMP-2 expression was associated with the nodular sclerosis subtype, and its expression was most pronounced in the vicinity of sclerosis. Neither of the gelatinases nor the extent of neovascularization correlated with tumor stage, the occurence of bulky disease, or extranodal infiltrates. Together, these findings imply that the adverse role of MMP-9 may be associated with the controlling of immunological processes but not the invasion prob- abilities or neovascularization of the tumor. The favorable prognostic value of MMP-2 is surprising in view of the role of MMPs in solid tumors. This, however, may be linked to the basic biological differences of hematological malignancies vs. other tumors. Outi Kuittinen 1 , Ylermi Soini 2 , Taina Turpeenniemi-Hujanen 1 1 Department of Oncology and Radiotherapy, and 2 Department of Pathology, Oulu University Hospital, Oulu, Finland Key words: Hodgkin's disease; MMP-2; MMP-9; invasion; prognostic factors; prognosis; neovascularization Correspondence: Professor Taina Turpeenniemi- Hujanen, Oulu University Hospital, Department of Oncology and Radiotherapy, Kajaanintie 50, 90220 Oulu, Finland Fax: + 3580 8315 6449 Accepted for publication 2 October 2002 Eur J Haematol 2002: 69: 205–212 Printed in UK. All rights reserved Copyright Ó Blackwell Munksgaard 2002 EUROPEAN JOURNAL OF HAEMATOLOGY ISSN 0902-4441 205