Expression of protein C (PC), protein S (PS) and thrombomodulin (TM) in human colorectal cancer

• Published in: Thrombosis research Vol. 125; no. 3; pp. e71 - e75
• Main Authors: Sierko, Ewa, Wojtukiewicz, Marek Z, Zawadzki, Roman, Zimnoch, Lech, Kisiel, Walter
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2010
• Subjects: Adult; Anticoagulants - metabolism; Coagulation inhibitor; Colon cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Male; Middle Aged; Protein C; Protein C - metabolism; Protein S; Protein S - metabolism; Rectal cancer; Thrombomodulin; Thrombomodulin - metabolism; ABC; PS; G; gelatinase A, matrix metalloproteinase -2; EC(s); IRS; protein S; N; number; TLTR; Colon cancer; protein C; small cell lung cancer; thromboembolic episodes; “tethered ligand” thrombin receptor; SCLC; colorectal cancer; PAR-1; Rectal cancer; EGF; protease activated receptor-1; Coagulation inhibitor; avidin biotin complex technique; TE; immunoreactive score; PC; APC; MMP-2; CRC; endothelial cell(s); grade; thrombomodulin; TM; EPCR; epidermal growth factor; endothelial cell protein C receptor; activated protein C; Protein C; Protein S; Thrombomodulin
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2009.09.011

Abstract Introduction Colorectal cancer (CRC) is often complicated by thromboembolic episodes. It has been recognized that blood coagulation proteins play a role in cancer progression. An important inhibitory mechanism is provided by the protein C (PC) system consisting of PC, protein S (PS) and thrombomodulin (TM). Recently, novel biological activities have been ascribed to the PC system that do not relate to their hemostatic functions, eg. in angiogenesis, apoptosis and inflammation. Objectives The purpose of the study was to elucidate the solid phase interactions between CRC tissue and components of the PC system that may contribute to tumor progression. Material and methods CRC tissues were obtained at surgical resection during treatment of 66 patients. Immunohistochemical studies were performed using polyclonal antibodies against PC, PS and TM. A semiquantitative analysis of the protein expression was also performed. Results Weak expression of PC was observed in cancer cells of two-thirds of the specimens examined, while in 3/66 cases there was no staining for PC in cancer cells. One fourth of CRCs exhibited strong expression of PC. The presence of PS was demonstrated in 64/66 cases of CRC. However, its expression was irregular in terms of intensity of staining and percentage of cancer cells exhibiting protein expression. Weak expression of TM was demonstrated in two thirds of the cases examined, while a strong TM staining was revealed in one third of colon cancers. Conclusion Heterogeneous expression of the PC system components in CRC tissue may point to their biological activity modulating tumor growth.