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

Background: . Colorectal carcinoma (CRC) is one of the major causes of cancer death worldwide. Data fromthe literature indicate differences between the proliferation rate of endothelial cells relative to the morphologygrowth 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 isexpressed in more than 90% of cases of metastatic CRC. Aim: The aim of this study was to evaluate the endothelialcell 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 CRCcases. CD34/ Ki67 double immunostaining and RNA scope assay for VEGF were performed.
Results: In theprimary tumors analysis of VEGFmRNA expression indicated no significant correlation with differentiationgrade, proliferative and non-proliferative vessels in the intratumoral and peritumoral areas. In contrast, in thecorresponding liver metastases, VEGFmRNA expression significantly correlated with the total number of nonproliferativevessels and total number of vessels. CD34/ Ki67 double immunostaining in the cases with poorlydifferentiated carcinoma indicated a high number of proliferating endothelial cells in the peritumoral area anda low number in the intratumoral area for the primary tumor. Moderately differentiated carcinomas of colonshowed no proliferating endothelial cells in the intratumoral area in half of the cases included in the study, forboth, primary tumor and liver metastasis. In well differentiated CRCs, in primary tumors, a high proliferationrate 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 endothelialcells in half of the cases for the primary tumors and liver metastases in moderately differentiated carcinomasuggest a vascular mimicry phenomenon. The mismatch between the total number of vessels and endothelialproliferation in primary tumors indicate that a functional vascular network is already formed or the existenceof some mechanisms influenced by other angiogenic factors.