Co-localization of Coagulation Factor X and its Inhibitory System, PZ/ZPI, in Human Endometrial Cancer Tissue

Abstract

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...

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“… 21 , 22 Similar results were also observed for endometrial cancer. 23 Moreover, for gastric cancer, the mRNA expression of PROZ was detected in gastric cancer cells and not in normal tissues. 24 Factors X and PZ have been demonstrated to be colocalized in gastric cancer tissues.…”

Effect of 3D laparoscopy versus traditional laparotomy on serum tumor markers and coagulation function in patients with early-stage endometrial cancer

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