Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer and Corresponding Liver Metastases

  • Raluca, Balica Amalia (Department of Histology, Angiogenesis Research Center) ;
  • Cimpean, Anca Maria (Department of Histology, Angiogenesis Research Center) ;
  • Cioca, Andreea (Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy) ;
  • Cretu, Octavian (Department of Surgery, "Victor Babes" University of Medicine and Pharmacy) ;
  • Mederle, Ovidiu (Department of Histology, Angiogenesis Research Center) ;
  • Ciolofan, Alexandru (Department of Surgery, "Victor Babes" University of Medicine and Pharmacy) ;
  • Gaje, Pusa (Department of Histology, Angiogenesis Research Center) ;
  • Raica, Marius (Department of Histology, Angiogenesis Research Center)
  • Published : 2015.06.26


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. Aim: The aim of this study was to evaluate the endothelial cell proliferation and VEGF expression in primary tumors and corresponding liver metastases. Materials and 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.


Colon carcinoma;endothelial cell proliferation;metastasis


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