Expression of Protein Z-Dependent Protease Inhibitor (ZPI) In Situ in Different Malignant Tumors.

Abstract

Cancer progression is often associated with thromboembolic complications. Coagulation factors and inhibitors influence various processes involved in malignant tumor growth and metastatic dissemination. Recently a new coagulation inhibitor - protein Z-dependent protease inhibitor (ZPI) has been characterized. ZPI is a plasma proteinase inhibitor in the serpin superfamily. ZPI inhibits factor Xa activity in the presence of calcium and phospholipids. Protein Z augments its activity by more than 1000-fold. ZPI also attenuates the activity of factor XIa in the reaction which does not require the presence of calcium and phospholipids. ZPI inhibits the coagulation response prior to the formation of the prothrombinase complex. Up to now the data on the presence of ZPI in malignant tumors are obscure. The purpose of the study was to elucidate the solid phase interactions between various types of maligant tissues and ZPI that may contribute to tumor progression. The tissues from colon, breast, gastric, renal, pancreatic, endometrial carcinoma, non-small cell lung cancer (NSCLC) as well as from glial neoplasms were obtained at surgical resection during radical treatment. The patients undergoing surgery have not received any previous antineoplastic therapy. Tumor fragments were processed acc. to AMeX method and then embedded in paraffin. Immunohistochemical studies (avidin-biotin complex-ABC - technique) were performed using a monoclonal antibody against ZPI. Expression of ZPI was observed in cancer cell bodies of colon, breast, gastric, renal, endometrial, pancreatic cancer, NSCLC and glial neoplasms. The staining intensity for ZPI was irregular: both strong and weak expression of ZPI was observed. Moreover, various percentages of ZPI-positive cancer cells were revealed in different specimens of examined tissues. Macrophages and mucin also revealed expression of ZPI in the case of colon cancer. The presence of ZPI was demonstrated in the stroma of renal cancer. The obtained results suggest that ZPI being an inhibitor of coagulation might additionally play a role in the regulation of cancer progression.