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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 immunohistochemistry 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% (66-83%) 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.

Original publication




Journal article


Clin Cancer Res

Publication Date





7144 - 7149


Adult, Aged, Aged, 80 and over, Antigens, CD34, Breast Neoplasms, Disease-Free Survival, Endothelium, Female, Glycoproteins, Humans, Hyaluronan Receptors, Immunohistochemistry, Lymphatic Vessels, Middle Aged, Multivariate Analysis, Neoplasm Metastasis, Platelet Endothelial Cell Adhesion Molecule-1, Prognosis, Time Factors, Treatment Outcome, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3, Vesicular Transport Proteins