Expression of Ephb2 And Ephb4 in Breast Carcinoma

Qinghua WU1, Zhenhe SUO1, Bjorn RISBERG1, Mats G KARLSSON2, Kenneth VILLMAN3, Jahn M NESLAND1

1Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway
2Department of Pathology, Örebro Medical Center Hospital, Örebro, Sweden
3Department of Oncology, Örebro Medical Center Hospital, Örebro, Sweden


Eph receptor tyrosine kinases and their cell-surfacebound ligands, the ephrins, play key roles in diverse biological processes. Eph receptors comprise the largest family of receptor tyrosine kinases consisting of eight EphA receptors (with five corresponding ephrinA ligands) and six EphB receptors (with three corresponding transmembrane ephrinB ligands). Originally identified as neuronal pathfinding molecules, EphB receptors and ephrinB ligands are later proved to be crucial regulators of vasculogenesis and embryogenesis. More studies indicate that Eph receptors are involved in angiogenesis and tumorigenesis. This study aimed to investigate the expression of EphB2 and EphB4 in breast carcinomas. Semiquantitative RT-PCR and immunohistochemistry were used to examine the expression patterns of EphB2 and EphB4. Clinicopathological and survival correlations were statistically analyzed in a series of 94 breast carcinomas, 9 normal specimens and 4 breast carcinoma cell lines. 1(1%), 16(17%), 29(31%), 48(51%) of the 94 tumors were negative, weak, moderate and strong EphB2 protein expression, respectively. 6(6%), 27(29%), 28(30%), 33(35%) of the tumors were negative, weak, moderate and strong EphB4 expression, respectively. Both EphB2 and EphB4 RTPCR products could be detected in all specimens. Increased EphB2 protein expression was negatively associated with overall survival, and there was a trend that increased EphB2 protein expression was correlated with shorter disease free survival, while EphB4 protein expression was associated with histological grade and stage. EphB4 membrane staining was increased with S phase fraction and associated with DNA aneuploidy. These findings indicate that both EphB2 and EphB4 are involved in the development of breast cancer and that both molecules could be potential predictive markers. Pathology & Oncology Research, Vol 10, Nr 1, 26-33, 2004

Key words: EphB2; EphB4; breast carcinoma; RT-PCR; immunohistochemistry

Received: Feb 11, 2004; accepted: Feb 25, 2004
Correspondence: Zhenhe SUO, Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo N-0310, Norway; Tel: +47 22065588, Fax: +47 22730164; E-mail:

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