title: Expression of the c-kit receptor characterizes a subset of neuroblastomas with favorable prognosis.
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.
authors.affiliation: Department of Pediatric Pathology, University of Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Krams
authors.forename: Reza
authors.initials: R
authors.lastname: Parwaresch
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Klaus
authors.initials: K
authors.lastname: Heidorn
authors.forename: Dieter
authors.initials: D
authors.lastname: Harms
authors.forename: Pierre
authors.initials: P
authors.lastname: Rudolph
mesh_terms: D002454:Cell Differentiation; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit