Angiogenesis in pituitary adenomas.

Angiogenesis, which is the formation of new blood vessels from preexisting capillaries, plays an important role in tumor growth and metastasis. In this review, the focus is on angiogenesis in pituitary adenomas. Angiogenesis of pituitary adenomas has been assessed by studying tumor microvessel density using specific immunohistochemical markers to clarify the relationship between angiogenesis and tumor behavior. Unlike other organs, pituitary adenomas have significantly lower vascular densities as compared to nontumorous adenohypophysis, suggesting that the lack of significant angiogenesis may play a role in the slow pace of pituitary tumor growth and rarity of metastases. In addition, the relationship between microvessel density and various factors in pituitary adenomas is reviewed, including tumor types, age and sex, invasiveness, malignancy, several proliferative markers (MIB-1 or Ki-67). However, further studies will be needed, since many studies have reached opposite conclusions. Angiogenesis is a complex multistep process and several factors are found to be involved in each step of neovascularization, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and various other cytokines. VEGF and bFGF (or FGF-2), which are the most potent angiogenesis inducers among them, have been studied by immunohistochemistry, in situ hybridization, or in vitro studies in normal or adenomatous pituitaries and these results are also discussed in this review. Copyright 2003 Wiley-Liss, Inc.