ACTIVITY OF TYPE-IV COLLAGENASES IN BENIGN AND MALIGNANT BREAST DISEASE

Using zymography and computer assisted image analysis, we have measure d the levels of type IV collagenases in biopsies from normal breast, a nd 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 tum ours, four of 12 grade II tumours, but 11 of 11 grade III tumours. Mea n 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 toget her, 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 diseas e (P = 0.003). There was also a trend towards a higher proportion of a ctive enzyme with increasing tumour grade (P<0.0001). In situ hybridis ation and immunohistochemistry studies showed that that mRNA and prote in for the 92 kDa enzyme was primarily found in the tumour stroma. mRN A for the 72 kDa enzyme was also found in stromal areas. This study de monstrates a clear relationship between production of Type IV collagen ases and malignant breast disease. Inhibitors of these enzymes may be of value in preventing metastatic disease.