Activity of type IV collagenases in benign and malignant breast disease.

Using zymography and computer assisted image analysis, we have measured the levels of type IV collagenases in biopsies from normal breast, and benign and malignant breast disease. The 92 kDa form was present in three of 11 cases of normal/benign disease, three of nine grade I tumours, four of 12 grade II tumours, but 11 of 11 grade III tumours. Mean levels were higher in grade III tumours (P < 0.0001). When the levels of 72 kDa collagenase and its active 62 kDa form were considered together, there was no difference between the benign and malignant cases (P = 0.55), but the amount of active enzyme, considered as a proportion of the 62 + 72 kDa forms, was significantly higher in malignant disease (P = 0.003). There was also a trend towards a higher proportion of active enzyme with increasing tumour grade (P < 0.0001). In situ hybridisation and immunohistochemistry studies showed that that mRNA and protein for the 92 kDa enzyme was primarily found in the tumour stroma. mRNA for the 72 kDa enzyme was also found in stromal areas. This study demonstrates a clear relationship between production of Type IV collagenases and malignant breast disease. Inhibitors of these enzymes may be of value in preventing metastatic disease.