Members of the Eph family of
receptor tyrosine kinase have been implicated in cell-cell communication and tissue integrity during embryogenesis. We have previously demonstrated cell type specific and
hormone dependent EphB4 expression in the mouse mammary parenchyma suggesting involvement in the homeostasis of this organ. Since disruption of tissue organization is crucial for metastatic dissemination, we have investigated the expression of EphB4 during
carcinogenesis of the human breast. Immunohistochemical analysis of 24 normal human breast samples and 124 consecutive
breast carcinomas was correlated with
tumor characteristics (stage, histology, grade, lymph node involvement) and the expression of ER, PR, Ki-67, p53 and HER2. In normal breast tissue, the
EphB4 protein was expressed exclusively in parenchymal cells. Strikingly, a drastic reduction in the number of
EphB4 protein expressing cells was observed in almost all invasive
carcinomas analyzed, irrespective of the
tumor type (p<0.0001). Furthermore, we found a highly significant correlation between EphB4 positivity and low histological grading of the
tumor cells (p=0.002) suggesting that in
breast cancer, EphB4 expression is not compatible with
tumor progression. This raises the possibility that EphB4 could represent a potent tool for therapeutic intervention.