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

Oncogene volume 23, pages 588–595 (2004)Cite this article

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 (P<0.0001), and portended a favorable outcome with a relative risk of 0.18 (P<0.0001). In a multivariate analysis of event-free survival, loss of c-kit (relative risk 4.25, P<0.0001) was an independent prognostic factor next to INSS stage 4 and before MYCN 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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Acknowledgements

This work was supported by grants from the Kinder Krebs Initiative, Buchholz Holm-Seppensen, Germany, and the Else Kröner-Fresenius Stiftung, Bad Homburg, Germany. We thank Professor Holger Kalthoff for the opportunity to perform LightCycler analyses in his laboratory.

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Authors and Affiliations

  1. Department of Pediatric Pathology, University of Kiel, Germany

    Matthias Krams & Dieter Harms

  2. Department of Hematopathology, University of Kiel, Germany

    Reza Parwaresch & Klaus Heidorn

  3. Department of General Pathology, University of Kiel, Germany

    Bence Sipos & Pierre Rudolph

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  1. Matthias Krams
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  2. Reza Parwaresch
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Correspondence to Pierre Rudolph.

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Krams, M., Parwaresch, R., Sipos, B. et al. Expression of the c-kit receptor characterizes a subset of neuroblastomas with favorable prognosis. Oncogene 23, 588–595 (2004). https://doi.org/10.1038/sj.onc.1207145

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