Plasminogen activators and their inhibitor gene expression in cutaneous NF1-related neurofibromas

Abstract

Cutaneous neurofibromatosis 1 (NF1)-related neurofibromas are benign tumors and composed of Schwann cells, perineurial cells and/or fibroblasts, endothelial cells, mast cells and macrophages. Extracellular proteolysis namely plasminogen activation (PA) operates in many tissue destructive processes. We wanted to study plasminogen activators, urokinase (uPA) and tissue type (tPA) and their inhibitor PAI-1, which have not earlier been studied comprehensively in cutaneous NF1-related tumors. We analyzed the distribution of uPA, tPA and PAI-1 antigen level by immunohistochemistry and mRNA level by in situ hybridization, to identify which cells are primarily involved in proteolytic activity and plasminogen activation. Twelve NF1 skin tumor samples from six patients were obtained during the operations. Mast cells, macrophages and endothelial cells were distributed only locally. Their expression levels of PA components were not so notable. Large extent of tumor cells of Schwann cell origin and prominent expression levels of uPA, tPA and PAI-1 indicated that these cells are responsible for the main source of PA components in cutaneous NF1-related neurofibromas.