Influence of Tumoral Microvessel Density on the Recurrence-Free Survival in Human Breast Cancer: Preliminary Results

Abstract

Background: Angioneogenesis is known to be a key step in the metastatic process of solid malignant tumors. Recently published data suggest a prognostic influence of angiogenetic activity on the clinical outcome of patients with breast cancer. In the present analysis, we evaluated the prognostic effect of tumoral microvessel density on the recurrence-free survival in human breast cancer. Patients and Methods: The tumoral vessel density was examined for its prognostic relevance to 5-year disease-free survival in 64 patients with primary breast cancer. Immunocytochemical staining for factor-VIII-related antigen was performed to visualize neovascular endothelial cells. Using an ocular raster, we distinguished vessels (forming lumina) and sprouts (singular endothelial cells). Results: In patients with a peritumoral vessel density of more than ten vessels per raster, we found a probability of 5-year recurrence-free survival of 42.7%, whereas a density of less than ten vessels implied an increased probability of 87.8% (log-rank test: p = 0.0011). Although a high tumoral vessel density was associated with a positive lymph node status and histologically undifferentiated tumors, lymph node status and vessel density seemed to be independent prognostic factors in the Cox model. The amount of endothelial sprouts, however, showed no prognostic relevance in the multivariate analysis. Thus, the distinction of vessels and sprouts proved to be useful for the prognostic outcome. 6 out of 18 node-negative patients with high vessel density experienced recurrence of the disease, but none out of 14 node-negative patients with a low vessel density showed a tumor relapse within 5 years after diagnosis. Conclusion: Thus we conclude that the assessment of tumoral vessel density might be a useful prognostic factor to distinguish more accurately between high- and very-low-risk node-negative breast cancer patients.