PLASMA ASSAY OF GELATINASE-B - TISSUE INHIBITOR OF METALLOPROTEINASE COMPLEXES IN CANCER

Background, Matrix metalloproteinases (MMPs), especially gelatinase A and gelatinase B (GLB), are believed to be important components of the metastatic process, Tissue Inhibitors of Metalloproteinases (TIMPs) f orm complexes with MMPs and inhibit cancer dissemination, After local secretion, MMPs and their complexes with TIMPs leach into the blood st ream where their concentration can be measured, thereby serving as sur rogate markers of disease. Elevated plasma gelatinase B levels have be en detected in gastrointestinal cancer and breast cancer, The goal of this study was to determine whether plasma GLB:TIMP complexes also are increased in cancer and whether these tests have potential use as pro gnostic tumor markers. Methods, An enzyme-linked immunosorbent assay ( ELISA) was developed to measure the plasma concentration of GLB:TIMP c omplexes in patients with cancer, Correlation between ELISA results an d clinical outcome was sought. Results, Plasma GLB:TIMP complexes were significantly increased in patients with gastrointestinal cancer and gynecologic cancer, but not in patients with breast cancer. When resul ts from plasma GLB:TIMP complexes and plasma GLB assays were combined (GLB/complexes), abnormal levels of one or both assays were found in 3 6% and 65% of patients with gastrointestinal and gynecologic cancer, r espectively, In Stage IV gastrointestinal cancer, patient survival was shorter (P < 0.001) in the group with increased plasma GLB/complexes than for those with normal plasma levels (4 months vs. 20 months, resp ectively). Conclusions, The assay of plasma gelatinase B and GLB:TIMP complexes may be clinically useful in predicting survival in subsets o f patients with cancer. The possibility of using these assays in early stage cancer to predict metastasis should be studied.