Expression of the c-kit receptor characterizes a subset of neuroblastomas with favorable prognosis

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Abstract
Expression of the c-kit proto-oncogene product in neuroblastomas has been reported, but its clinical relevance is unclear. We determined the expression of c-kit by immunohistochemistry in a series of 155 neuroblastomas with long-term follow-up. The specificity of the reaction was verified by Western blot analysis and quantitative RT–PCR, and exon 11 of the kit gene was screened for mutations by PCR and capillary electrophoresis. No mutations were detected, and transcription of the kit gene correlated with protein expression. c-kit expression was associated with lower tumor stages and a low rate of MYCN amplification. More importantly, it coincided with tumor differentiation (PPPMYCN amplification. It is concluded that c-kit is transcriptionally regulated in neuroblastomas. Its expression likely identifies a subset of neuroblastomas with conserved capacity for differentiation, which may represent the embryonal variety of the disease. Assessment of c-kit may improve prognostic models for neuroblastoma and provide a basis for new therapy concepts.

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