EXPRESSION OF MESSENGER-RNA FOR THE NEUROTROPHIN RECEPTOR TRKC IN NEUROBLASTOMAS WITH FAVORABLE TUMOR STAGE AND GOOD PROGNOSIS

Childhood neuroblastoma rumours of the sympathetic nervous system show a remarkable clinical heterogeneity ranging from spontaneous regressi on to unfavourable outcome despite intensive therapy. Favourable neuro blastomas often express high levels of trkA mRNA, encoding the tyrosin e kinase receptor for nerve growth factor. We have investigated mRNA e xpression for the neurotrophin receptor trkC in 23 primary neuroblasto mas using a sensitive RNAase protection assay. TrkC expression was det ected in 19 of these rumours al highly variable levels with a 300-fold difference between the highest and lowest values. Significantly highe r levels of trkC mRNA were found in tumours from patients with favoura ble features such as low age (P < 0.012), favourable tumour stage (P < 0.012) and favourable prognosis (P < 0.05). Children with intermediat e or high trkC mRNA expression had better prognosis compared with thos e with low or undetectable levels (83.3% vs 20%: P = 0.005). Further c haracterisation of trkC mRNA expression by reverse transcriptase-polym erase chain reaction (RT-PCR) showed that mRNA encoding the full-lengt h cytoplasmic tyrosine kinase domain of the receptor was only expresse d in a subset of favourable tumours. These data show that favourable n euroblastomas may express the full trkC receptor while advanced rumour s, in particular MYCN-amplified neuroblastoma, seem to either express no trkC or truncated trkC receptors of as yet unknown biological funct ion. These data are suggestive of a role for trkC and its preferred li gand neutotrophin-3, NT-3, in neuroblastoma differentiation and/or reg ression.