EXPRESSION OF TRKA, TRKB AND TRKC IN HUMAN NEUROBLASTOMAS

There is considerable interest in the role of the TRK family of neurot rophin receptors in regulating the survival, growth and differentiatio n of normal and neoplastic nerve cells. Indeed, there is increasing ev idence that TRK genes play an important role in the biology and clinic al behavior of neuroblastomas, tumors of the peripheral nervous system . Evidence from several independent studies suggests that high express ion of TrkA is an indicator of favorable outcome, and there is an inve rse correlation between TrkA expression and N-myc amplification. In ad dition, some primary neuroblastomas differentiate in vitro in the pres ence of NGF but die in its absence. We have evidence that coexpression of full-length TrkB and BDNF is associated with N-myc amplification a nd may represent an autocrine survival pathway. Conversely, truncated TrkB is expressed predominantly in differentiated tumors. Finally, Trk C is expressed in favorable neuroblastomas, essentially all of which a lso express TrkA. In summary, the study of neurotrophin receptor expre ssion and function in neuroblastomas may provide important insights in to the role that these pathways play in the pathogenesis and clinical behavior of this tumor. Ultimately, these pathways may provide attract ive targets for the development of therapy aimed at inducing different iation or programmed cell death in these tumors.