Enhanced expression of EphrinB1 is associated with lymph node metastasis and poor prognosis in breast cancer

BACKGROUND: The Eph family of receptor tyrosine kinases and their ephrin ligands are membrane-bound cell-signaling proteins and they play critical regulatory roles in embryonic development and carcinogenesis. Eph receptors require direct cell to cell interaction for activation and they are divided into EphA and EphB receptor classes, depending on their preferential binding affinity for EphrinA or EphrinB ligands. Eph receptors have been documented in breast cancer, but the Ephrin ligands have not been thoroughly investigated. MATERIALS AND METHODS: We conducted a systematic assessment of EphrinB1 expression in a set of 75 formalin-fixed paraffin-embedded breast cancers, using immunohistochemical staining (IHC) with a specific antibody, and we examined the relationship between EphrinB1 expression, histopathological parameters, and the expression of estrogen (ER), progesterone (PR), and HER-2 receptors. RESULTS: High level expression of EphrinB1 is positively associated with lymph node metastasis (P < 0.0001) and with the presence of HER-2 receptor (P = 0.041) and it is more often detected in triple-negative breast carcinomas (P = 0.038). No relation was apparent between EphrinB1 expression level and other histopathological parameters, but enhanced EphrinB1 expression is associated with shorter overall survival (P = 0.015). CONCLUSION: Our analysis demonstrates that EphrinB1 expression is related to the metastasis of breast cancer and its enhanced expression confers a poor prognosis, suggesting that EphrinB1 may be a relevant therapeutic target in breast cancers.