Expression of vascular endothelial growth factor and its receptor Flk-1 in human neuroblastoma using in situ hybridization.
OBJECTIVE
Although angiogenic factors may play an important role in the biology of neuroblastoma, which frequently spreads hematogenously, the mechanism remains unclear. The authors studied tumor progression and invasion from the perspective of angiogenesis and sought to understand the features of this type of tumor.


METHODS
Thirty-one specimens were resected from patients with neuroblastoma and the expression of vascular endothelial growth factor (VEGF), and its receptor (Flk-1) was examined using immunohistochemistry. The authors looked for correlations among the expressions of VEGF and its receptor with various clinicopathologic factors. In addition, they examined the expression and location of VEGF and Flk-1 mRNA in 10 primary neuroblastoma using in situ hybridization.


RESULTS
Both in situ hybridization and immunohistochemistry showed the presence of VEGF expression within the neuroblastoma cells. We found VEGF mRNA in neuroblastoma cells but not vascular endothelial cells according to in situ hybridization. Further, Flk-1 mRNA was present both in neuroblastoma cells and vascular endothelial cells. The level of VEGF expression was higher in unfavorable histology, using the criteria of Shimada, than in favorable histology.


CONCLUSIONS
The authors suggest that paracrine and autocrine systems are involved in the angiogenesis of neuroblastoma, and the expression of VEGF correlates with the prognosis in neuroblastoma.
Fukuzawa
Masahiro
M
First Department of Surgery, Nihon University School of Medicine, Tokyo, Japan.
Sugiura
Hiroaki
H
Koshinaga
Tsugumichi
T
Ikeda
Taro
T
Hagiwara
Noritugu
N
Sawada
Tatsuo
T
D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D008222:Lymphokines / Q000032:analysis* / Q000235:genetics; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology; D009447:Neuroblastoma / Q000737:chemistry* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis*; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040301:Vascular Endothelial Growth Factor Receptor-2