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

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.