COEXPRESSION OF MESSENGER-RNA FOR THE FULL-LENGTH NEUROTROPHIN RECEPTOR TRK-C AND TRK-A IN FAVORABLE NEUROBLASTOMA

Neuroblastoma, a childhood tumour of the sympathetic nervous system, m ay sometimes regress spontaneously in infants, or progress to a poor c linical outcome despite intensive therapy. Neuroblastomas express neur otrophin receptors and high levels of mRNA for trk-A correlates with f avourable outcome, whereas trk-B mRNA is expressed by more unfavourabl e tumours. Using a sensitive RNase protection assay, mRNA expression f or the neurotrophin receptor trk-C was investigated in 50 tumour sampl es from 45 children at different stages including metastatic and relap sing tumour tissue, out of which 22 were also investigated for trk-A m RNA. Thirty-seven of 43 primary tumours (86%) showed trk-C mRNA with m ore than 300-fold difference between the highest and the lowest values . A higher trk-C index (trk-C mRNA/GAPDH mRNA) was associated with fav ourable features such as younger age (P = 0.009-0.003), favourable tum our stage (1, 2 or 4S; P < 0.001) and favourable prognosis (P = 0.044) . Better survival probability was shown in children with intermediate or high trk-C index compared with patients with low or undetectable le vels (P = 0.031). All localised tumours co-expressed mRNA for trk-A an d trk-C receptors. RT-PCR analysis detected mRNA encoding the cytoplas mic trk-C tyrosine kinase region only in favourable neuroblastomas. We conclude that favourable neuroblastoma may express the full-length tr k-C receptor while unfavourable tumours, especially those with MYCN am plification, seem to either express no trk-C or truncated trk-C recept ors with unknown biological function. Trk-C and possibly its preferred ligand NT-3 may be involved in the biology of favourable neuroblastom as showing apoptosis or differentiation. (C) 1997 Elsevier Science Ltd .