Ret-oncogene expression correlates with neuronal differentiation of neuroblastic tumors

An antibody to the ret proto-oncogene product (RET) was raised and applied to formalin-fixed, paraffin-embedded neuroblastic tumors (NBTs) to investigate its usefulness in diagnosis and evaluation of cell differentiation. In normal neural crest-derived tissues, most ganglion cells were moderately stained while large ganglion cells were weakly stained. In NBTs, the intensity of the staining in moderately differentiated neuroblasts and small ganglion cells was more prominent than in undifferentiated neuroblasts, while the cytoplasm of large ganglionic cells was weakly stained as in normal ganglion cells. The RET immunoreactivity was compared with that of nine neural and neuroendocrine markers. The results revealed a parallelism with the protein gene product 9.5 (PGP9.5), neuron specific enolase (NSE) and NF-150 kD (NF = M). These findings indicated that the RET immunoreactivity was correlated with ganglionic differentiation and maturation. Thus, RET was considered to be a new marker that would be implemented in diagnosis and estimation of neuronal differentiation of NBTs.