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Expression of KIT receptor tyrosine kinase in endothelial cells of juvenile brain tumors.

Puputti M, Tynninen O, Pernilä P, Salmi M, Jalkanen S, Paetau A, Sihto H, Joensuu H - Brain Pathol. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Helsinki Biomedical Graduate School, Helsinki, Finland.

ABSTRACT
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.

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Ependymoma showing strong (+++) endothelial cell KIT expression in the tumor vessels (A; original magnification ×200, ×400 in inset) and in microvascular proliferations (B; ×200). (C) Ependymoma with strong expression of phosphorylated KIT in tumor endothelial cells (×400). KIT mRNA in tumor microvessel endothelial cells (D) detected by in situ hybridization (×400, arrows).
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fig03: Ependymoma showing strong (+++) endothelial cell KIT expression in the tumor vessels (A; original magnification ×200, ×400 in inset) and in microvascular proliferations (B; ×200). (C) Ependymoma with strong expression of phosphorylated KIT in tumor endothelial cells (×400). KIT mRNA in tumor microvessel endothelial cells (D) detected by in situ hybridization (×400, arrows).

Mentions: To investigate whether tumor endothelial cells might express KIT, SCF or VEGFR-2 also in other types of pediatric brain tumors than pilocytic astrocytoma, we examined 49 further tumors with immunohistochemistry (Tables 3 and 4). Marked (++ or +++) expression of KIT and phospho-KIT were frequently present in the endothelia of ependymomas [6 (55%) out of 11, and 5 (45%) out of 11, respectively]. Anaplastic ependymomas had glomeruloid microvascular proliferations resembling those seen in glioblastomas. Staining for KIT was positive in the endothelial cell cytoplasm of delicate capillaries (Figure 3A) and microvascular proliferations (Figure 3B). Occasional abluminal cells stained positively for KIT in the microvascular proliferations, although the staining intensity was lower than in endothelial cells lining the vessel lumens (Figure 3B). In anaplastic ependymomas endothelial cells and most of the abluminal cells of microvascular proliferations stained positively for phosphorylated KIT with uniform intensity (Figure 3C). Age at diagnosis and KIT expression in tumor endothelial cells had a similar association in ependymomas as in pilocytic astrocytomas, although this association was not statistically significant (P = 0.067, Mann–Whitney test; P = 0.33 Kruskal–Wallis test; Figure 2, lower panel).


Expression of KIT receptor tyrosine kinase in endothelial cells of juvenile brain tumors.

Puputti M, Tynninen O, Pernilä P, Salmi M, Jalkanen S, Paetau A, Sihto H, Joensuu H - Brain Pathol. (2009)

Ependymoma showing strong (+++) endothelial cell KIT expression in the tumor vessels (A; original magnification ×200, ×400 in inset) and in microvascular proliferations (B; ×200). (C) Ependymoma with strong expression of phosphorylated KIT in tumor endothelial cells (×400). KIT mRNA in tumor microvessel endothelial cells (D) detected by in situ hybridization (×400, arrows).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2901521&req=5

fig03: Ependymoma showing strong (+++) endothelial cell KIT expression in the tumor vessels (A; original magnification ×200, ×400 in inset) and in microvascular proliferations (B; ×200). (C) Ependymoma with strong expression of phosphorylated KIT in tumor endothelial cells (×400). KIT mRNA in tumor microvessel endothelial cells (D) detected by in situ hybridization (×400, arrows).
Mentions: To investigate whether tumor endothelial cells might express KIT, SCF or VEGFR-2 also in other types of pediatric brain tumors than pilocytic astrocytoma, we examined 49 further tumors with immunohistochemistry (Tables 3 and 4). Marked (++ or +++) expression of KIT and phospho-KIT were frequently present in the endothelia of ependymomas [6 (55%) out of 11, and 5 (45%) out of 11, respectively]. Anaplastic ependymomas had glomeruloid microvascular proliferations resembling those seen in glioblastomas. Staining for KIT was positive in the endothelial cell cytoplasm of delicate capillaries (Figure 3A) and microvascular proliferations (Figure 3B). Occasional abluminal cells stained positively for KIT in the microvascular proliferations, although the staining intensity was lower than in endothelial cells lining the vessel lumens (Figure 3B). In anaplastic ependymomas endothelial cells and most of the abluminal cells of microvascular proliferations stained positively for phosphorylated KIT with uniform intensity (Figure 3C). Age at diagnosis and KIT expression in tumor endothelial cells had a similar association in ependymomas as in pilocytic astrocytomas, although this association was not statistically significant (P = 0.067, Mann–Whitney test; P = 0.33 Kruskal–Wallis test; Figure 2, lower panel).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Helsinki Biomedical Graduate School, Helsinki, Finland.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus