High LYVE-1 positive lymphatic vessel numbers are associated with axillary lymph node metastases and poor outcome in breast cancer

Abstract

9518 Background: 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 which is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues. Methods: We investigated expression of LYVE-1 by means of immunhistoochemistry in a series of 180 unilateral, invasive ductal breast carcinomas, in order to assess the correlation between the density of lymph vessels, the incidence of lymph node metastases and clinical outcome. Results: A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No significant association was found between the number of LYVE-1 positive vessels and the number of CD31 or VEGFR-3 (vascular endothelial growth factor receptor-3) positive vessels. 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 (DDFS) and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% CI, 46 to 70%) 5-year DDFS as compared with 74% (66 to 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 the presence of frequent axillary node metastases and a poor outcome in invasive ductal breast cancer. No significant financial relationships to disclose.