Immunohistochemical localization of coagulation, fibrinolytic and antifibrinolytic markers in adenocarcinoma of the lung

Abstract

Extravascular coagulation and fibrinolysis are intimately involved in and modulate cancer cell growth, invasion and metastasis. Samples from resection specimens of patients with primary lung cancer (adenocarcinomas) were tested with monoclonal (MAb) and polyclonal (PAb) antibodies against various factors of the coagulation or fibrinolysis systems, or against antigens of inflammatory or proliferating cells. MAb Ki-67 specific to nuclear antigens of proliferating cells showed a distinct but variable staining of cell nuclei throughout the tumor tissue. Nests of tumor tissue stained with cytokeratin-specific antibodies (PKK1), whereas other parts were negative. Fibrin(ogen) and fibronectin were found throughout the tumor tissue stroma and in the alveolar lining, and the most densely stained areas were at the transition zone between normal and tumor tissue. Fibrinolytic system components like tissue plasminogen activators (t-PA), and urokinase (u-PA), and their inhibitors PAI-1 and PAI-2 were all studied. All specimens were negative for t-PA (except endothelial linings), whereas urokinase-specific antibodies stained loosely packed tumor cells and macrophages within the tumor stromal tissue and alveolar septa. Both PAI-1 and PAI-2 were most prominently expressed within interstitial and alveolar macrophages. A weaker staining of tumor tissue cells was demonstrated. Inflammatory cells like macrophages and T lymphocytes were located in aggregates or diffusely spread within tumor stromal tissue. The inflammatory reaction was most intense at the border between normal lung and tumor tissue.