Expression of KIT receptor tyrosine kinase in endothelial cells of juvenile brain tumors.
KIT receptor tyrosine kinase is expressed in tumor endothelial cells of adult glioblastomas, but its expression in pediatric brain tumor endothelial cells is unknown. We assessed expression of KIT, phosphorylated KIT, stem cell factor (SCF) and vascular endothelial growth factor receptor-2 (VEGFR-2) in 35 juvenile pilocytic astrocytomas and 49 other pediatric brain tumors using immunohistochemistry, and KIT messenger RNA (mRNA) using in situ hybridization. KIT and phospho-KIT were moderately or strongly expressed in tumor endothelia of 37% and 35% of pilocytic astrocytomas, respectively, whereas marked SCF and VEGFR-2 expression was uncommon. KIT mRNA was detected in tumor endothelial cells. Tumor endothelial cell KIT expression was strongly (P < 0.01) associated with endothelial cell phospho-KIT and SCF expression, and with tumor KIT (P = 0.0011) and VEGFR-2 expression (P = 0.022). KIT and phospho-KIT were present in endothelia of other pediatric brain tumors, notably ependymomas. Endothelial cell KIT expression was associated with a young age at diagnosis of pilocytic astrocytoma or ependymoma, and it was occasionally present in histologically normal tissue of the fetus and children. We conclude that KIT is commonly present in endothelial cells of juvenile brain tumors and thus may play a role in angiogenesis in these neoplasms.
Puputti
Marjut
M
Helsinki Biomedical Graduate School, Helsinki, Finland.
Tynninen
Olli
O
Pernilä
Paula
P
Salmi
Marko
M
Jalkanen
Sirpa
S
Paetau
Anders
A
Sihto
Harri
H
Joensuu
Heikki
H
D000293:Adolescent; D000367:Age Factors; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004806:Ependymoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D010766:Phosphorylation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2