Assessment of tumor vascularization: immunohistochemical and non-invasive methods

Growth of solid tumors beyond a certain mass is dependent on the vascular bed from pre-existing host vasculature. The process of angiogenesis is essential not only for primary tumor growth but also for metastasis. The number of microvessels within the invasive component of a primary tumor reflects the degree of tumor angiogenesis. At present the most widely used method to assess neovascularization is the quantitation of intratumoral microvessel density (IMD) by immunohistochemical methods in which specific markers for endothelial cells are employed. In this paper we analyze the different methods used to assess IMD, as well as their advantages and potential methodological pitfalls. Several studies have shown a close correlation between IMD, tumor growth and the occurrence of metastasis, suggesting that IMD is a prognostic indicator of clinical relevance. Furthermore, preliminary studies suggest that determination of angiogenesis may predict responsiveness to some forms of conventional anticancer therapy. Although the histological microvessel density technique is the current gold standard to characterize tumor angiogenesis, it may not be the ideal tool for clinical purposes because it needs to be performed on biopsy material and does not assess the functional pathways involved in the angiogenic activity of tumors. Non-invasive assessment of tumor vascularity is possible in vivo by means of Doppler sonography, dynamic contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography (PET). These methods may be preferable to histological assay because they are non-invasive, survey the entire tumor, reflect both anatomic and physiologic characteristics, and may be useful to monitor the activity of antiangiogenic therapies.