title: Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.
abstract: BACKGROUND
  Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF).
  
  
  OBJECTIVE
  The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco.
  
  
  METHODS
  G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR).
  
  
  RESULTS
  Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs.
  
  
  CONCLUSIONS
  The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.
authors.affiliation: Department of Oncology, Medical University of Bialystok, Poland.|Comprehensive Cancer Center, Białystok, Poland.
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
authors.affiliation: Department of Oncology, Medical University of Bialystok, Poland.|Comprehensive Cancer Center, Białystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sierko
authors.affiliation: Department of Oncology, Medical University of Bialystok, Poland.|Comprehensive Cancer Center, Białystok, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Skalij
authors.affiliation: Department of Oncology, Medical University of Bialystok, Poland.|Comprehensive Cancer Center, Białystok, Poland.
authors.forename: Magda
authors.initials: M
authors.lastname: Kamińska
authors.affiliation: Department of Pathomorphology, Medical University of Bialystok, Poland.
authors.forename: Lech
authors.initials: L
authors.lastname: Zimnoch
authors.affiliation: Department of Pharmacology, UT-Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Brekken
authors.affiliation: Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thorpe
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011485:Protein Binding; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: breast cancer; granulocyte colony stimulating factor; neutropenia; tissue factor; vascular endothelial growth factor receptor