Lymphatic Microvessel Density, VEGF-C, and VEGFR-3 Expression in Different Molecular Types of Breast Cancer.

摘要

BACKGROUND: Breast cancer is a heterogeneous disease and five major distinct molecular types have been characterized by gene analysis and immunohistochemistry. The molecular types of breast cancer have different behavior, a particular profile of response to therapy, reflected in the differential survival of patients. Previous findings showed a particular preference for lymph node and distant metastases of different molecular types, but the specific lymphangiogenic profile of these types is lacking. PATIENTS AND METHODS: We investigated the differential expression vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and D2-40 by immunohistochemistry, to evaluate lymphangiogenesis and the lymphatic microvessel density (LMVD), in patients with breast cancer, stratified according to the molecular classification. RESULTS: There was a differential expression of VEGF-C/VEGFR-3 and D2-40 in different molecular types of breast cancer, with highest level of expression for these markers being found in HER2 and luminal B types and the lowest in basal-like type. The lowest value of both intratumoral and peritumoral LMVD were found in normal-like type breast cancer. VEGF-C expression did not correlate with the grade of the tumor, but a significant correlation was found with lymph node metastasis. VEGFR-3 expression was found in 66.66% of the cases and correlated with the expression of VEGF-C in tumor cells. There was a positive correlation between VEGF-C, VEGFR-3 and LMVD only in the HER2 type, and a positive correlation in HER2 and normal-like types with VEGFR-3 expression in tumor cells. In addition, there was a correlation between HER2 type, VEGF-C and VEGFR-3 expression in tumor cells and lymphatic endothelium, respectively, and LMVD. CONCLUSION: Our results support a differential signature of lymphangiogenesis in different molecular types of breast cancer and these findings may have a direct impact on prognosis and therapeutic strategy of this disease.