Microscopic Assessment of Angiogenesis in Tumors

Although it has been recognized for many centuries that neoplastic tissue is more vascular than its normal counterpart, it is only since Folkmans’ hypothesis on antiangiogenesis (1 ) that a more quantitative method for measuring angiogenesis in tissue sections has been pursued. Folkman and colleagues recognized that quantitation of the tumor vasculature might play an important a role in predicting tumor behavior and patient management. They therefore developed a microscopic angiogenesis grading system, designated the “MAGS” score, calculated by measuring vessel number, endothelial cell hyperplasia, and cytology in tinctorially stained tissue sections (2 ). It was hoped that this would be an objective method for quantifying tumor angiogenesis, one that would yield important information on the relationship to other clinicopathological tumor characteristics and help in the testing of antiangiogenic therapies. However, although it was possible to classify tumors into endothelial “poor” or “rich,” the technical limitations of sample selection, inter- and intra-observer variation, and conceptual biological problems were such that the technique could not be easily applied. Interest in grading tumor angiogenesis was rekindled in the 1980s with the advent of nonspecific endothelial markers (3 –5 ), but only in the last five to ten years, with the advent of more specific endothelial markers, have quantitation studies on tissues have been performed.