Departments of Neurosurgery and Neurology, New York University, School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Neuro Oncol. 2010 Feb;12(2):122-32. doi: 10.1093/neuonc/nop044. Epub 2010 Jan 25.
Nuclear factor IA (NFIA) is a transcription factor that specifies glial cell identity and promotes astrocyte differentiation during embryonic development. Its expression and function in gliomas are not known. Here, we examined NFIA protein expression in gliomas and its association with clinical outcome in pediatric malignant astrocytomas. We analyzed expression of NFIA by immunohistochemistry in 88 existing glioma specimens from Childrens Hospital Los Angeles and the University of Southern California. Association between NFIA expression and progression-free survival (PFS) was examined in high-grade astrocytomas for which clinical data were available (n = 23, all children). NFIA was highly expressed in astrocytomas of all grades, but only in a minority of cells in oligodendroglial tumors. NFIA was expressed on a higher percentage of tumor cells in low-grade astrocytomas (91 +/- 5% and 77 +/- 14% in World Health Organization [WHO] I and II, respectively) compared with high-grade astrocytomas (48 +/- 18% and 37 +/- 16% in WHO III and IV, respectively; P < .001, low- vs high-grade astrocytomas). There was a significant association between NFIA expression and PFS in children with astrocytoma WHO grade III or IV (Cox regression P = .019; logrank trend test for NFIA tertiles P = .0040 and NFIA quartiles P = .014). The association was not consistently significant in this small series of patients after adjustment was made for WHO grade III or IV. This is the first study to demonstrate expression of NFIA protein in astrocytomas and its association with grades of astrocytoma and PFS, suggesting that NFIA may play a role in astrocytoma biology.
核因子 IA(NFIA)是一种转录因子,它决定神经胶质细胞的特征,并在胚胎发育过程中促进星形胶质细胞的分化。其在神经胶质瘤中的表达和功能尚不清楚。在这里,我们检查了 NFIA 蛋白在神经胶质瘤中的表达及其与小儿恶性星形细胞瘤临床结果的关系。我们通过免疫组织化学分析了洛杉矶儿童医院和南加州大学现有的 88 例神经胶质瘤标本中的 NFIA 表达。对于具有临床数据的高级别星形细胞瘤(n = 23,均为儿童),我们检查了 NFIA 表达与无进展生存期(PFS)之间的关联。NFIA 在所有级别星形细胞瘤中均高度表达,但在少突胶质细胞瘤中仅在少数细胞中表达。NFIA 在低级别星形细胞瘤中的肿瘤细胞中表达比例更高(分别为 WHO I 和 II 级中的 91 +/- 5%和 77 +/- 14%),与高级别星形细胞瘤相比(分别为 WHO III 和 IV 级中的 48 +/- 18%和 37 +/- 16%;P <.001,低级别 vs 高级别星形细胞瘤)。在 WHO 分级为 III 或 IV 的星形细胞瘤患儿中,NFIA 表达与 PFS 之间存在显著相关性(Cox 回归 P =.019;NFIA 三分位组的对数秩趋势检验 P =.0040,四分位组 P =.014)。在对 WHO 分级 III 或 IV 进行调整后,在这个小系列患者中,这种关联并不始终具有统计学意义。这是第一项研究表明 NFIA 蛋白在星形细胞瘤中的表达及其与星形细胞瘤分级和 PFS 的关系,表明 NFIA 可能在星形细胞瘤生物学中发挥作用。