Angiogenesis is essential for
tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of
tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/
factor VIII staining) and the degree of pericyte coverage [by alpha-smooth muscle actin (alpha-SMA)/
factor VIII staining], in a large and population-based series of
endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these
tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [
vascular endothelial growth factor (
VEGF)-A,
VEGF-C,
VEGF-D and
basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive
tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the alpha-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by
tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive
tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of
endometrial carcinoma.