High LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer

Purpose: The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium-specific hyaluronan receptor, is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues. Experimental Design: We investigated expression of LYVE-1 by immunhistochemistry in 180 unilateral, invasive ductal breast carcinomas and assessed the presence and density of lymph vessels within the tumor and at the tumor periphery. Results: A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No substantial association was found between the number of LYVE-1-positive vessels and the number of CD31 or vascular endothelial growth factor receptor-3-positive vessels, or vascular endothelial growth factor-C expression. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P = 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% confidence interval, 46-70%) 5-year distant disease-free survival as compared with 74% (6683%) among those with a low peritumoral lymph vessel density (P = 0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis. Conclusions: A high peritumoral lymph vessel density is associated with a poor outcome in ductal breast cancer.