TRK AND RET PROTOONCOGENE EXPRESSION IN HUMAN NEUROBLASTOMA SPECIMENS- HIGH-FREQUENCY OF TRK EXPRESSION IN NON-ADVANCED STAGES

Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto- oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve gro wth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stag es and in patients with favorable prognosis according to the Shimada c lassification. Moreover, trk expression inversely correlated with Nmyc -gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngtR (low-affinity N GF receptor)-gene expression was present in 9 out of 25 cases. The sim ultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF. (C) 1993 Wiley-Liss, Inc.