Gelatinases (MMP-2 and MMP-9), TIMP-1 expression and the extent of neovascularization in aggressive non-Hodgkin's lymphomas

• Published in: European journal of haematology Vol. 71; no. 2; pp. 91 - 99
• Main Authors: Kuittinen, Outi, Apaja-Sarkkinen, Meeri, Turpeenniemi-Hujanen, Taina
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.08.2003; Blackwell
• Subjects: Biological and medical sciences; Biomarkers - analysis; collagenase; Collagenases - analysis; Disease Progression; factor VIII; Factor VIII - analysis; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; invasion; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - diagnosis; Lymphoma, Non-Hodgkin - enzymology; Lymphoma, Non-Hodgkin - mortality; matrix metalloproteinase; Matrix Metalloproteinase 2 - analysis; Matrix Metalloproteinase 9 - analysis; Medical sciences; Neovascularization, Pathologic - diagnosis; Neovascularization, Pathologic - enzymology; non-Hodgkin's lymphoma; Prognosis; prognostic factors; Survival Analysis; TIMP-1; Tissue Inhibitor of Metalloproteinase-1 - analysis; Human; Prognosis; TIMP-1; Enzyme; Tissue inhibitor metalloproteinase 2; Factor VIII; Tissue inhibitor metalloproteinase 1; Metalloendopeptidases; Malignant hemopathy; prognostic factors; Non Hodgkin lymphoma; Gelatinase B; Invasion; Gelatinase A; Peptidases; collagenase; non-Hodgkin's lymphoma; Lymphoproliferative syndrome; Hydrolases; matrix metalloproteinase; Neovascularization; Interstitial collagenase; High malignancy
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1034/j.1600-0609.2003.00101.x

: Objectives:  The present study was carried out to clarify the role of matrix metalloproteinase‐2 and ‐9 (MMP‐2 and MMP‐9), tissue inhibitor of metalloproteinase‐1 (TIMP‐1) and the extent of neovascularization in the clinicopathologic behavior of non‐Hodgkin's lymphomas. Methods:  Paraffin‐embedded histologic sections from 57 patients with aggressive non‐Hodgkin's lymphomas were stained with MMP‐2, MMP‐9, TIMP‐1, and factor VIII antibodies to correlate the expression of these markers to the clinical disease characteristics. Results:  Strong MMP‐9 staining was found to be an adverse prognostic factor among patients with aggressive B‐cell lymphomas, the probabilities for 5‐yr disease‐free survival being 73%, 63%, 50%, and 0% in patients with grades 0, 1, 2, and 3 staining, respectively. Among the patients with strong (grades 2 and 3) MMP‐9 staining, however, positivity for TIMP‐1 indicated a trend toward a more favorable prognosis. TIMP‐1 expression also correlated with the immunoblastic and anaplastic lymphoma subtypes. The expression of the proteins for MMP‐2 and factor VIII had no independent prognostic role. None of the study parameters correlated with disease stage, the occurrence of extranodal infiltrates, the occurrence of bulky tumor, or the IPI scores. Conclusions:  Positivity for MMP‐9 immunoreactive protein is an independent sign of an unfavorable prognosis in non‐Hodgkin's lymphomas. This is not mediated through influences in tumor dissemination or neovascularization indicating it to carry other important biological functions.