Expression of Matrix Metalloproteinase and Tissue Inhibitors of Matrix Metalloproteinase in Malignant Lymphoma

ABSTRACT

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix. The balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumors. Although MMP and TIMP are believed to play an important role in invasion and metastasis in malignant solid tumors, little is known about their involvement in malignant lymphoma. Immunohistochemical stains for MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were performed using 56 paraffin blocks of the malignant lymphoma and the results were analyzed by using the tumor grade by Working Formulation. The expression of MMP-9 was noted in 45.5% of low grade, 86.1% of intermediate grade, and 100% of high grade malignant lymphoma. The incidence of MMP-9 expression in tumor cells was positively correlated with the grade of the malignant lymphoma (P<0.025). In nodal lymphomas, the incidence of the MMP-9 expression of the tumor cells was higher in malignant lymphoma with extracapsular invasion than those without extracapsular invasion (P=0.008). The incidence of TIMP-1 expression in the tumor cells and fibroblasts was positively correlated with the grade of the malignant lymphoma (P<0.025). In nodal lymphoma, the incidence of the TIMP-1 expression of the tumor cells was higher in malignant lymphoma with extracapsular invasion than those without extracapsular invasion (P=0.009). The incidences of the MMP-1, MMP-2, and TIMP-2 expression in malignant lymphoma were neither increased in the malignant lymphoma with extracapsular tumor invasion nor correlated with the grade by working formulation. There was no significant difference in the expression rate of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in nodal- and extra-nodal malignant lymphoma. The above results suggest that the expressions of MMP-9 and TIMP-1 are positively correlated with the grade and the presence of extranodal tumor invasion in malignant lymphomas.