Expression of Protein Z (PZ) and Protein Z-Dependent Protease Inhibitor (ZPI) In Situ in Human Malignant Tissues.

The activity of the hemostatic system components facilitates tumor growth and dissemination. There exists a mechanism of direct inhibition of factor Xa that involves protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) system. ZPI also attenuates the activity of factor XIa. Data on the presence of PZ and ZPI in malignant tissue in situ are lacking.

The aim of this study was to assess the localization of PZ and ZPI in situ in colon, breast, gastric, laryngeal, pancreatic, renal, endometrial cancer, non-small cell lung cancer (NSCLC), malignant melanoma and glial neoplasms. Studies were performed on tumor tissues obtained at surgical treatment of previously untreated patients. Immunohistochemical procedures according to the ABC method and Envision Double Staining System (Dako) employed a polyclonal antibody against PZ and a monoclonal antibody against ZPI. Protein Z was localized in cancer cell bodies in all types of malignant tumors examined. Staining intensity was more pronounced in less differentiated cancer cells of anaplastic gliomas. In contrast, more differentiated cancer cells of gastric cancer revealed stronger staining than less malignant ones. Cancer cell bodies of NSCLC and renal cancer were characterized by weak intensity of staining for PZ. In pancreatic and renal cancer, as well as in malignant melanoma, the intensity of staining for PZ in cancer cells was irregular: both high and low PZ expression was observed independently of the degree of malignancy. Protein Z was also revealed in association with macrophages in colon cancer, NSCLC and malignant melanoma. Expression of ZPI was observed in cancer cell bodies in all examined specimens. The staining intensity for ZPI was irregular: both strong and weak expression of ZPI was observed. Various percentages of ZPI-positive cancer cells were observed in different specimens of the tissues examined. In colon cancer, ZPI expression was detected in tumor infiltrating macrophages. Double staining studies revealed co-expression of both proteins in cancer cell bodies in all examined tumor types, although there were areas of tumor foci where only one protein (either ZP or ZPI) was localized. Our results suggest that PZ and ZPI, apart from being inhibitors of blood coagulation, may play an additional regulatory role in tumor progression.