title: Kit expression in spindle cell rhabdomyosarcoma can possibly create a different approach for its tumorigenesis and therapy.
abstract: The use of a relatively nontoxic tyrosine kinase receptor inhibitor, imatinib mesylate (IM) (STI-571), has increasingly become a valuable therapeutic alternative in some KIT (CD117)-overexpressing neoplasms potentially because of the presence of KIT-activating mutations. As the treatment eligibility for this drug hinges on CD117 expression, KIT immunostaining has recently been widely examined in various different tumors. We examined CD117 expression in pediatric embryonal rhabdomyosarcomas (RMSs) to identify its eventual prognostic impact and to evaluate its effect on tumorigenesis. This study included two spindle cell (leiomyomatous) variants, two botryoid variants, and 21 conventional embryonal RMSs. Sections from paraffin-embedded tumor samples were immunostained by a standard SABC technique using c-kit polyclonal antibody with antigen retrieval. In all the series, the percentage of CD117 positivity was 12%. Staining was strong in two of two spindle cell variants, in zero of two botryoid variants, and in one of 21 conventional embryonal RMSs. In Spearman's correlation analysis, there was statistical relationship between the presence of CD117 expression and the histological subtype of RMS. Kaplan-Meier analysis revealed no prognostic significance of CD117 expression for survival. The present study demonstrated a very limited expression of CD117 in pediatric embryonal RMS other than in the spindle cell variant. This finding suggested that the stem cell factor/c-kit pathway may be implicated in the tumorigenesis of spindle cell RMSs. Therefore, the mutation of c-kit gene must be prospectively examined in larger series of RMSs. If it can be verified that tissue expression of CD117 reflects the mutation of c-kit gene, IM can be considered a targeted therapy for CD117-expressing RMSs, particularly the spindle cell variant.
authors.affiliation: Pathology and Pediatric Oncology/Hematology Department, Izmir Dr.Behcet Uz Children's Hospital, Turkey. agdiniz@kablonet.com.tr
authors.forename: Gulden
authors.initials: G
authors.lastname: Diniz
authors.forename: Safiye
authors.initials: S
authors.lastname: Aktas
authors.forename: Ragip
authors.initials: R
authors.lastname: Ortac
authors.forename: Mine
authors.initials: M
authors.lastname: Tunakan
authors.forename: Ismet
authors.initials: I
authors.lastname: Unlu
authors.forename: Canan
authors.initials: C
authors.lastname: Vergin
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D018233:Rhabdomyosarcoma, Embryonal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit