High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer

Studies from model systems suggest that matrix metalloproteinases (MMPs) ar e causally involved in tumor progression while tissue inhibitors of MMPs (T IMPs) prevent this progression. Here, we show that concentrations of TIMP-I are significantly higher in breast carcinomas than in fibroadenomas. In pr imary breast cancers, TIMP-I concentrations increased with increasing tumor size but showed an inverse relationship with estrogen receptor concentrati ons. In primary breast cancers also, TIMP-I levels were weakly but signific antly correlated with those for MMP-1, proMMP-2, active MMP-2, MMP-3 and pr oMMP-9. Contrary to what might be expected from published data on model sys tems, high concentrations of TIMP-I predicted a poor outcome in patients wi th breast cancer. We conclude that in human breast cancer, endogenous TIMP- I does not inhibit tumor progression but may enhance the process, (C) 1999 Wiley-Liss, Inc.