IMMUNOHISTOLOGIC EVALUATION OF INVASION-ASSOCIATED PROTEASES IN BREAST-CARCINOMA

Immunostaining of two invasion-associated proteolytic enzymes, catheps in D (CD) and urokinase-type plasminogen activator (uPA), was assessed in cryostat sections of 86 stage-heterogeneous breast carcinomas usin g monoclonal antibodies. Most tumors displayed a focal and/or heteroge neous staining pattern. Overall, staining was more frequent in host-de rived stromal and inflammatory cells (uPA 54%, CD 89%) than neoplastic epithelium per se (uPA 24%, CD 70%). Intense (i.e., 2+) stromal, but not neoplastic, CD was significantly correlated with nodal or systemat ic metastases (node negative-10% versus node positive/systemic-33%, p = 0.04). Further, cumulative staining of more than one enzyme (CD + uP A) or more than one tumor component (stroma + epithelium) correlated w ith metastatic disease (no metastases-35% versus metastatic-72%, p = 0 .005). Neither stromal nor epithelial CD alone was significantly corre lated with short-term recurrence free survival, however additive CD st aining (i.e., stromal + epithelial) was strongly predictive, overall ( both + -75% recurred versus both weak/negative-16% recurred, p = 0.000 4) and in node positive patients (p = 0.02). We conclude that (a) enzy mes putatively mediating extracellular matrix dissolution may be deriv ed from multiple sources and (b) the metastatic capacity and/or clinic al aggressiveness of breast carcinomas may reflect overall proteolytic enzyme expression, suggesting that cooperative enzyme interaction may be required for invasive growth and/or metastasis.