Localization of 92-kDa Type IV Collagenase in Human Skin Tumors: Comparison with Normal Human Fetal and Adult Skin

Abstract

To investigate the role of secreted metalloproteinases in the behavior of skin tumors we have studied immunoreactivity for 92-kDa type IV collagenase (92T4Cl) in benign tumors of sweat glands, basal cell carcinomas (BCC), baso-squamous cell carcinomas (BSCC), and squamous cell carcinomas (SCC). In all tumors, the enzyme was found in stromal cells, but not in tumor epithelium. 92T4Cl-positive cells contained the common leukocyte antigen HLe-1(CD45) and the polymorphonuclear leukocyte-specific antigen PMN-8C7. Only a few 92T4Cl-positive cells expressed either macrophage-specific Leu-M5 or eosinophil-specific cationic protein antigens. In benign sweat gland tumors, and in the majority of nodulocystic and adenoid BCCs, 92T4Cl-positive cells were relatively rare and no extracellular deposition of the enzyme was found. In the more aggressive tumors examined, SCCs, BSCC, recurrent, infiltrative, and morpheaform BCCs, 92T4Cl-positive cells were very abundant. In addition, a significant quantity of extracellular enzyme was deposited both within the extracellular matrix adjacent to the tumor nests and in their basement membrane zone. In normal adult skin only a few scattered 92T4Cl-containing cells were found in the dermis whereas in fetal skin, groups of 92T4Cl-positive, HLe-1-negative cells were present in the upper dermis. These observations suggest that in cutaneous tumors, extensive infiltration of 92T4Cl containing polymorphonuclear leukocytes and the extracellular deposition of the enzyme in the basement membrane zone are signs of more aggressive tumor behavior.