title: Loss of EphB4 receptor tyrosine kinase protein expression during carcinogenesis of the human breast.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Univeristy Hospital, Inselspital Berne, Schanzeneckstrasse 1, Switzerland. gilles.berclaz@insel.ch
authors.forename: Gilles
authors.initials: G
authors.lastname: Berclaz
authors.forename: Bettina
authors.initials: B
authors.lastname: Flütsch
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Altermatt
authors.forename: Valeria
authors.initials: V
authors.lastname: Rohrbach
authors.forename: Valentin
authors.initials: V
authors.lastname: Djonov
authors.forename: Andrew
authors.initials: A
authors.lastname: Ziemiecki
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dreher
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Andres
mesh_terms: D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036224:Receptor, EphB4 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D036224:Receptor, EphB4