In this issue, Hollingsworth et a1l present evidence that increasing intratumor microvessel density in the areas of most intense neovascularization is associated with decreasing overall and disease-free survival in patients with advanced stage ovarian cancer. Moreover, using a Cox proportional hazards model, they showed that intratumor microvessel density may be a better predictor of disease-free survival than stage, grade, and tumor type, whereas stage was the best predictor of overall survival. The authors conclude that analysis of tumor neovascularization in advanced stage ovarian cancer may be a useful prognostic marker.

Clearly, for a tumor to grow, the tumor cells must not only proliferate, but benign host tissue, especially new blood vessels, must also form around the tumor cells. In 1971, Folkman proposed that tumor growth is dependent on angiogenesis. 2 Furthermore, he sug-gested that tumor cells and blood vessels composed a highly integrated ecosystem, that endothelial cells could be switched from a resting state to one of rapid growth by a diffusible signal from tumor cells or associated inflammatory cells, and that antiangiogenesis could be an effective anticancer therapy. Indeed, now there is considerable indirect and direct evi-dence to show that tumor growth is angiogenesis dependent, that tumor cells can produce diffusible angiogenic regulatory molecules, and that angiogenesis antagonists can slow or prevent tumor growth. The indirect evidence is that tumors, both in vitro and in vivo, that lack access to blood vessels will grow only until passive diffusion can no longer provide adequate nutrients or allow waste products to exit into the adjacent medium. 35 At equilibrium, these avascular spheroids reach sizes of only 4mm in vitro6 and