Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours

EphB2, a receptor tyrosine kinase regulated by the β-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the ApcMin/+ mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P=0.005), poor differentiation (P=