title: Protein Z/protein Z-dependent protease inhibitor system in human non-small-cell lung cancer tissue.
abstract: BACKGROUND
  NSCLC progression is often associated with VTE. Activation of factor X is an important step in blood coagulation activation in cancer patients. PZ)/ZPI contribute to direct factor Xa inhibition, and ZPI - attenuates factors IXa and XIa activity. The role of the PZ/ZPI in NSCLC is obscure. The aim of the study was to localize ZPI and PZ in NSCLC tissue in relation to factors X, IX and XI, as well as indicators of blood coagulation activation: prothrombin fragment F1+2 (F1+2) and fibrin.
  
  
  METHODS
  Immunohistochemical studies were performed on surgical NSCLC specimens employing antibodies against ZPI, PZ, coagulation factors X, IX, XI, as well as fibrinogen, F1+2 and fibrin. A semiquantitative analysis (acc. to immunoreactive score-IRS) was conducted.
  
  
  RESULTS
  Medium expression of ZPI(IRS=6.5), together with weak expression of PZ(IRS=4), was observed in cancer cells. Strong or medium staining for factors IX, X, and XI(IRS=8-9) was revealed in cancer cells. Fibrinogen(IRS=10) and fibrin(IRS=8) were demonstrated in tumor stroma and cancer cells. F1+2(IRS=10) was localized in NSCLC cells. Endothelial cells (ECs) and tumor infiltrating macrophages (TAMs) were characterized by a positive staining for ZPI and PZ.
  
  
  CONCLUSIONS
  ZPI and PZ expression in NSCLC cells, ECs and TAMs may suggest a role for PZ/ZPI in the anticoagulant mechanisms at the tumor site. The presence of F1+2 and fibrin, along with a disproportional expression of ZPI and PZ, might point to impaired function of the coagulation inhibitory system in NSCLC tissue.
authors.affiliation: Department of Oncology, Medical University, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sierko
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
authors.forename: Lech
authors.initials: L
authors.lastname: Zimnoch
authors.forename: Krystyna
authors.initials: K
authors.lastname: Ostrowska-Cichocka
authors.forename: Piotr
authors.initials: P
authors.lastname: Tokajuk
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Walter
authors.initials: W
authors.lastname: Kisiel
mesh_terms: D001779:Blood Coagulation Factors / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D001779:Blood Coagulation Factors; D001798:Blood Proteins; C416370:SERPINA10 protein, human; D015843:Serpins; C026080:plasma protein Z