Angiogenesis and endometrial cancer.
Angiogenesis occurs more frequently in endometrial carcinomas developing against a background of endometrial atrophy rather than carcinomas arising from a hyperplastic endometrium. In some studies, angiogenesis is associated with unfavourable histopathological features, but not in others. In all studies, however, increased angiogenesis is related to poor prognosis. Vascular endothelial growth factor (VEGF) is the major stimulus for endothelial cell proliferation in endometrial carcinomas and is, therefore, associated with high angiogenesis. VEGF expression at the invading tumour front is 4-10 times higher than in the inner tumour areas and is significantly associated with poor prognosis, particularly within stage I endometrial disease. However, since its stimulating effect on endothelial cells is basically dependent on the presence of VEGF receptors, i.e. the flk-1(KDR), the detection of a functionally intact angiogenic pathway VEGF/flk-1 (KDR) is a more reliable and, indeed, independent prognostic parameter. The other angiogenic factor, thymidine phosphorylase (TP), is related to the adverse histopathological variables of the non endometrioid carcinomas, high tumour grade, deep myometrial invasion and advanced stage of disease, at least at the invading tumour front, and its prognostic significance is, therefore, limited. Furthermore, it is not directly related with increased angiogenesis. However, the simultaneous expression of high VEGF / high TP activity at the invading tumour front emerged as the most potent angiogenic phenotype in endometrial carcinomas, indicating that the two molecules are co-operating. Furthermore, a high TP activity in the stromal cells is associated with a high density of activated macrophages which further promotes endometrial tumour angiogenesis.
Sivridis
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Department of Pathology, Democritus University of Thrace, Alexandroupolis, Greece. esivrid@med.duth.gr
D000818:Animals; D016889:Endometrial Neoplasms / Q000098:blood supply*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D013939:Thymidine Phosphorylase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013939:Thymidine Phosphorylase