Tumor Angiogenesis – factors influencing the development of a tumor vascular network and assessment of neoangiogenesis in histopathological samples

Abstract

Angiogenesis involves the formation of capillaries on the basis of already existing blood vessels. It is a multi-stage process resultant from the combined influence of pro- and anti-angiogenic factors. It begins with the stimulation of endothelial cells and degeneration of the basilemma and extracellular matrix, followed by the proliferation of endothelial cells and eventually the formation of a new vessel. The final stage involves a synthesis of the vessel's basilemma and incorporation of pericytes stabilizing the capillary tube. Any study of angiogenesis necessitates a direct assessment of tissue vascularisation and indirect assessment of the occurrence of pro-angiogenic factors. The degree of vascularisation is determined on the basis of the number of capillaries and endothelial cell concentrations per a surface unit of a given tissue or organ. The same is achieved by staining histopathological samples with immunohistochemical methods using panendothelial antibodies: anti FVIII, anti-CD31 and anti CD34. The antibodies identifying proliferating endotelial cells are also specific to the evaluation of neoangiogenesis. The same include monoclonal antibodies: E9 and TEC-11. The quantitative analysis of blood vessel density in tumor tissue (MVD - microvessel density) is performed with the Weidner method. The total microvascular area (TVA) is also considered a significant angiogenic factor. The assessment of the relative surface area of capillaries within a tumor is performed using Chalkley's method, vessel branching count (VBC) and angiogenic index. Indirect methods of angiogenesis assessment involve the determination of angiogenic cytokine production and the expression of their cellular receptors. The study of modulators and assessment of angiogenesis may facilitate more efficient tumor diagnostics and therapy.