Markers of tumor angiogenesis: Clinical applications in prognosis and anti-angiogenic therapy

Numerous studies in many tumor types have demonstrated that quantitation by microvessel as a measure of angiogenesis is a powerful prognostic tool. However, the ability to exploit tumor angiogenesis as a prognostic marker is limited by the methods currently used for capillary identification and quantitation. This report critically evaluates all aspects of the techniques and their associated problems used for assessing tumor angiogenesis in tissue sections including the area of tumor assessed, the vascular parameter measured, the method of quantitation, the stratification of patients and the practical utility of computer image analysis systems. The potential of angiogenic factors assays, proteolytic enzymes, and cell adhesion molecules as surrogate endpoints for quantifying tumor angiogenesis are discussed and other methods for quantifying tumor angiogenesis are described. The potential clinical applications of these angiogenic markers in prognosis, stratification for adjuvant treatments (both cytotoxic and anti-angiogenic/vascular targeting) and other aspects of patient management is also discussed, particularly design of phase I and II trials.