ABSTRACT

Angiogenesis, the sprouting of new capillaries from existing blood vessels, and vasculogenesis, the de novo generation of blood vessels are the two primary methods of vascular expansion by which nutrient supply to tissues is adjusted to match physiological needs. Pathological angiogenesis is critical for growth and metastasis of malignant tumors (1). Conventionally, the vascularity of tissues has been assessed directly by microvessel density (MVD) counting after immunostaining with variety of panendothelial antibodies (2). This technique requires extracted tissue material and so is unable to provide information on the functional state of the vasculature. More recently, indirect or surrogate methods such as blood levels of angiogenic factors and imaging methods have been used to assess neovasculature (3). Advantages of indirect methods include the fact that they can be quantitative, noninvasive, and can be performed with the tumor in situ, and in the case of imaging techniques, the functional status of the vasculature can be assessed. In this respect it is important to note that implanted tumor xenograft data show that there is a discrepancy between perfused and visible microvessels; a variable 20% to 85% of microvessels are perfused at any given time. This results in a difference between histological MVD and what is described as the ‘‘true or functional vascular density’’, which at least in part accounts for the discrepancy between imaging and histological assessments of vascularity (4).