title: Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Histology and Molecular Pathology, Angiogenesis Research Center Timisoara, Victor Babes University of Medicine and Pharmacy, Romania. raica@umft.ro
authors: Marius
authors: M
authors: Raica
authors: Anca Maria
authors: AM
authors: Cimpean
authors: Raluca
authors: R
authors: Ceausu
authors: Domenico
authors: D
authors: Ribatti