Puputti Marjut, Tynninen Olli, Pernilä Paula, Salmi Marko, Jalkanen Sirpa, Paetau Anders, Sihto Harri, Joensuu Heikki
Helsinki Biomedical Graduate School, Helsinki, Finland.
Brain Pathol. 2010 Jul;20(4):763-70. doi: 10.1111/j.1750-3639.2009.00357.x. Epub 2009 Nov 30.
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.
KIT受体酪氨酸激酶在成人生殖细胞瘤的肿瘤内皮细胞中表达,但其在儿童脑肿瘤内皮细胞中的表达情况尚不清楚。我们采用免疫组织化学方法评估了35例青少年毛细胞型星形细胞瘤和49例其他儿童脑肿瘤中KIT、磷酸化KIT、干细胞因子(SCF)和血管内皮生长因子受体2(VEGFR-2)的表达情况,并采用原位杂交技术检测了KIT信使核糖核酸(mRNA)。在37%的毛细胞型星形细胞瘤的肿瘤内皮细胞中,KIT和磷酸化KIT呈中度或强表达,分别占35%,而明显的SCF和VEGFR-2表达并不常见。在肿瘤内皮细胞中检测到KIT mRNA。肿瘤内皮细胞KIT表达与内皮细胞磷酸化KIT和SCF表达以及肿瘤KIT(P = 0.0011)和VEGFR-2表达(P = 0.022)密切相关(P < 0.01)。KIT和磷酸化KIT存在于其他儿童脑肿瘤的内皮细胞中,尤其是室管膜瘤。内皮细胞KIT表达与毛细胞型星形细胞瘤或室管膜瘤诊断时的年轻年龄相关,并且偶尔出现在胎儿和儿童的组织学正常组织中。我们得出结论,KIT通常存在于青少年脑肿瘤的内皮细胞中,因此可能在这些肿瘤的血管生成中发挥作用。