Expression of c-ErbB2 in human neuroblastoma tissues, adrenal medulla adjacent to tumor, and developing mouse neural...

We have examined the expression of c-ErbB2 in primary neuroblastoma tissues, mouse neural crest-derived tissues, and human adrenal gland adjacent to neuroblastoma tissue and of age-matched controls. c-ErbB2 expression was observed in approximately 60% of cases analyzed, and there were two staining patterns; one showed focal and cytoplasmic and the other showed diffuse and membrane staining patterns. The expression of c-ErbB2 in neuroblastoma tissues was confirmed by reverse transcription polymerase chain reaction and Western blot analysis. Diffuse and membrane staining of c-ErbB2 was well correlated with high urinary catecholamine secretion. In mouse tissues, cytoplasmic expression of c-ErbB2 was observed in immature peripheral neurons and adrenomedullary cells. In mature neurons, the immunoreactivity was confined to the plasma membrane. These results suggest that the expression of c-ErbB2 in neuroblastoma reflects the phenotype of developing peripheral neurons. Postnatal human and mouse adrenomedullary cells lacked c-ErbB2 immunoreactivity, although apparently normal adrenomedullary cells adjacent to neuroblastoma tissues showed strong cytoplasmic expression of c-ErbB2. It is not known whether the phenotypic conversion of adjacent adrenal medullary cells had occurred before or after tumor progression at present.