title: Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer and Corresponding Liver Metastases.
abstract: BACKGROUND
  . Colorectal carcinoma (CRC) is one of the major causes of cancer death worldwide. Data from the literature indicate differences between the proliferation rate of endothelial cells relative to the morphology growth type, possibly due to origin of specimens (autopsy material, surgery fragments) or quantification methods. Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of endothelial cells. It is expressed in more than 90% of cases of metastatic CRC.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the endothelial cell proliferation and VEGF expression in primary tumors and corresponding liver metastases.
  
  
  METHODS
  Our study included 24 recent biopsies of primary tumors and corresponding liver metastases of CRC cases. CD34/ Ki67 double immunostaining and RNA scope assay for VEGF were performed.
  
  
  RESULTS
  In the primary tumors analysis of VEGFmRNA expression indicated no significant correlation with differentiation grade, proliferative and non-proliferative vessels in the intratumoral and peritumoral areas. In contrast, in the corresponding liver metastases, VEGFmRNA expression significantly correlated with the total number of non- proliferative vessels and total number of vessels. CD34/ Ki67 double immunostaining in the cases with poorly differentiated carcinoma indicated a high number of proliferating endothelial cells in the peritumoral area and a low number in the intratumoral area for the primary tumor. Moderately differentiated carcinomas of colon showed no proliferating endothelial cells in the intratumoral area in half of the cases included in the study, for both, primary tumor and liver metastasis. In well differentiated CRCs, in primary tumors, a high proliferation rate of endothelial cells in the intratumoral area and a lower proliferation rate in the peritumoral area were found. A low value was found in corresponding liver metastasis.
  
  
  CONCLUSIONS
  The absence of proliferative endothelial cells in half of the cases for the primary tumors and liver metastases in moderately differentiated carcinoma suggest a vascular mimicry phenomenon. The mismatch between the total number of vessels and endothelial proliferation in primary tumors indicate that a functional vascular network is already formed or the existence of some mechanisms influenced by other angiogenic factors.
authors.affiliation: Department of Histology, Angiogenesis Research Center, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania E-mail : ancacimpean1972@yahoo.com.
authors.forename: Balica Amalia
authors.initials: BA
authors.lastname: Raluca
authors.forename: Anca Maria
authors.initials: AM
authors.lastname: Cimpean
authors.forename: Andreea
authors.initials: A
authors.lastname: Cioca
authors.forename: Octavian
authors.initials: O
authors.lastname: Cretu
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Mederle
authors.forename: Alexandru
authors.initials: A
authors.lastname: Ciolofan
authors.forename: Pusa
authors.initials: P
authors.lastname: Gaje
authors.forename: Marius
authors.initials: M
authors.lastname: Raica
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A