High-level expression of EPHB6, EFNB2, and EFNB3 is associated with low tumor stage and high TrkA expression in human neuroblastomas

Neuroblastoma (NB) is a common pediatric tumor of neural crest origin that is biologically and clinically heterogeneous. EPH family receptor tyrosine kinases and ephrin ligands play fundamental roles in neurodevelopmental pro cesses. Recently, we found that NE cell lines expressed several EPHB and EF NB transcripts, which encode EPHB subgroup receptors and ephrin-B subgroup ligands, respectively. To explore the role of EPHB receptors and ephrin-B l igands in the biology of NB, we examined the expression of EPHB and EFNB tr anscripts in 47 primary NE specimens. Multiple EPHB and EFNB transcripts we re expressed in all of the NE tumors examined, suggesting the involvement o f these transcripts in modulating the biological behavior of NE. Higher lev els of EPHB6, EFNB2, and EFNB3 expression were found in low-stage tumors (s tage 1, 2, and 4S) than in advanced-stage tumors (stage 3 and 4; P = 0.0013 , P = 0.0048, and P = 0.027, respectively). Expression of TrkA, a well-esta blished prognostic marker of favorable NB, was positively correlated with E PHB6, EFNB2, and EFNB3 expression (P < 0.0001, P = 0.0019, and P = 0.0001, respectively). MYCN-amplified tumors expressed lower levels of EPHB6, EFNB2 , EFNB3, and TrkA transcripts compared to nonamplified tumors (P = 0.0006, P = 0.0023, P = 0.0048, and P = 0.0001, respectively). These data suggest t hat high-level expression of EPHB6, EFNB2, and EFNB3 is associated with fav orable NE and that low-level expression of EPHB6, EFNB2, and EFNB3 correlat es with aggressive MYCN-amplified NB. Thus, EPHB6, EFNB2, and EFNB3 may hav e biological relevance in NE. Further investigation on the biology of these genes may help provide insight into the treatment of NE.