EXPRESSION OF METALLOPROTEINASES AND TISSUE INHIBITORS OF METALLOPROTEINASES IN GIANT-CELL TUMOR OF BONE - AN IMMUNOHISTOCHEMICAL STUDY WITH CLINICAL CORRELATION

The clinical behavior of giant cell tumors (GCTs) is unpredictable. To gain insight into this tumor's biological behavior, matrix metallopro teinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) we re studied. These substances play essential roles in wound healing and neoplastic invasion and metastasis. Paraffin-embedded, tissue iras co llected from 18 cases of histologically benign GCT, with 17 treated by curettage and 1 by resection. Eight cases showed no recurrence after a minimum of 2.5 years, and 10 had. local recurrence. One showed metas tasis. Antibodies to MMP-9, MMP-2, TIMP-1, and TIMP-2 were applied by immunohistochemical methods. In all cases, MMP-9 nas strongly expresse d in giant cells predominantly in a diffuse pattern and was strong but focal in stromal cells. MMP-2 decorated stromal cells and giant cells heterogeneously. TIMP-1 was variably expressed in giant cells of the nonrecurrent cases and was strongly present in a diffuse or patchy dis tribution in the stromal cells in 6 of 8 cases. However, in 9 of 10 re current cases, TIMP-1 was expressed weakly by both giant and stromal c ells. TIMP-2 was variably expressed in the giant cells of the nonrecur rent cases, but 6 of 8 nonrecurrent cases showed strong stromal cell p ositivity For TIMP-2. Weak staining for TIMP-2 was observed in 7 of 10 recurrent cases in the stromal cells and 9 of 10 recurrent cases in t he giant cells. These results indicate that expression of MMPs and TIM Ps differs in plant cells and stromal cells in the same tumor. More si gnificantly, in contrast to the nonrecurrent giant cell tumors, there is an imbalance in the MMPs and TIMPs in tile recurrent tumors with a net excess of MMPs. This unopposed expression of MMPs in GCTs may play a role in breakdown of extracellular matrix and tissue invasion. Fina lly, these markers may prove useful in predicting behavior in these tu mors. Copyright (C) 1996 by W.B. Saunders Company