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Dear Sirs, Breast cancer is one of the most frequently diagnosed malignancies in women worldwide (1). Haemostatic system alterations are commonly observed in breast cancer patients during the natural course of the disease or resulting from its antineoplastic treatment (2, 3). Furthermore, components of the coagulation cascade were documented to contribute to cancer progression (2-5). In malignancy activation of factor X was demonstrated to be triggered by numerous factors (2, 3). Thus, regulatory pathways which control factor Xa activity in cancer patients are of particular interest. A mechanism of direct inhibition of factor Xa activity involves the protein Z-dependent protease inhibitor (ZPI) and protein Z (PZ) system (6-8) with the latter acting as a co-factor (7, 8). Plasma ZPI circulates in complex with PZ (9). ZPI molecule is in approximately 25-35% homologous with members of serine protease inhibitors superfamily (7, 8). The data on ZPI presence in cancer tissue still remain obscure. The aim of the study was to evaluate presence of ZPI (both protein and mRNA) in loco in breast cancer tissue.

In gastric cancer, hemostatic system components contribute to cancer progression, as activation of factor X (FX) was observed. The protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) complex inhibits factor Xa proteolytic activity. The purpose of this study was to determine the distribution of ZPI and PZ in relation to FX, and prothrombin fragment (F1 + 2), a standard marker for blood coagulation activation, in human gastric cancer tissue. ABC procedures and a double staining method employed polyclonal antibodies against PZ, FX, and F1 + 2 and a monoclonal antibody against ZPI. In situ hybridization (ISH) methods employed biotin-labeled 25-nucleotide single-stranded DNA probes directed to either PZ or ZPI mRNAs. FX and components of PZ/ZPI coagulation inhibitory system were observed in cancer cells. F1 + 2 was observed in gastric cancer cells as well. Double staining studies revealed FX/PZ, FX/ZPI, and PZ/ZPI co-localization on gastric cancer cells. ISH studies demonstrated the presence of PZ mRNA and ZPI mRNA in gastric cancer cells indicating induced synthesis of these proteins. The co-localization of PZ/ZPI and FX in gastric cancer cells indicates in loco that these proteins may play a role in anticoagulant events at the tumor tissue.

Background/Aim: Hemostatic system components contribute to cancer progression independently from their roles in hemostasis. It has been shown that protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) inhibit coagulation factor X (FX). The aim of the study was to analyze the expression of PZ/ZPI in relation to the main coagulation factor-FX in human endometrial cancer tissue. Materials and Methods: Immunohistochemical analysis was performed on 21 endometrial cancer specimens employing antibodies against ZPI, PZ and FX. Results: Endometrial cancer cells showed a strong expression of ZPI and PZ and medium expression of FX. Normal endometrial tissue showed no expression of ZPI, PZ or FX. Conclusion: Strong expression of PZ and ZPI in endometrial cancer cells suggests a role of these proteins in endometrial cancer. The estimated global incidence of endometrial cancer is approximately 382,000 per year, and nearly 90,000 of women suffering from the disease die yearly, worldwide (1). Gynecological cancer is frequently associated with thromboembolic episodes (TE) (2). The complications (e.g. deep vein thromboembolism, portal vein thrombosis) may precede the diagnosis of the malignant disease and accompany the treatment (3, 4). Silent or subclinical venous thromboembolic complications (VTE) occur before treatment in approximately 10% of patients with endometrial cancer (5). Thromboembolic episodes may adversely complicate surgery, external beam radiotherapy, high-dose-rate brachytherapy, chemotherapy or hormonotherapy in gynecological cancer patients (6-10). In advanced stage of endometrial cancer disseminated intravascular coagulation has been reported as well (11). It has been reported that there are changes in coagulation factors prior to any treatment for endometrial cancer, suggesting that the disease may result in a procoagulant state (12, 13). Namely, increased levels of fibrinogen, thrombin-antithrombin complex (TAT), and prothrombin fragment F1+2 have been observed compared to non-cancer individuals (12, 13). One of the important steps of coagulation activation in cancer patients has been ascribed to the activation of factor X (FX) (14). Many cancer-specific stimuli have been recognized to trigger its activation, e.g. tissue factor (TF), cancer procoagulant (CP), procoagulant activity and platelet-aggregating activity (PCA/PAA), HLA-DR antigen of MHC (main human compatibility) class, as well as sialic acid residues of mucus glycoproteins, which are synthesized by cancer cells (14, 15). Numerous studies strongly suggest that the hemostatic system components contribute to cancer progression independently from their established roles in hemostasis (14, 16). Factor Xa stimulates cytokine synthesis in effector cells, activates nitrogen oxide synthase, induces adhesion molecule expression as well as the release of growth factors from endothelial cells (ECs) (17, 18). It can also activate endothelial protein C receptor (EPCR) and protease activated receptor-1, which are known to play a role in cancer growth and di...