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少突胶质细胞分化标志物在毛细胞型星形细胞瘤中的表达确定了两个临床亚组,并显示出与增殖指数和无进展生存期显著相关。

Expression of oligodendroglial differentiation markers in pilocytic astrocytomas identifies two clinical subsets and shows a significant correlation with proliferation index and progression free survival.

作者信息

Takei Hidehiro, Yogeswaren Subashini T, Wong Kwong-Kwok, Mehta Vidya, Chintagumpala Murali, Dauser Robert C, Lau Ching C, Adesina Adekunle M

机构信息

Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

出版信息

J Neurooncol. 2008 Jan;86(2):183-90. doi: 10.1007/s11060-007-9455-7. Epub 2007 Aug 10.

Abstract

The growth pattern of pilocytic astrocytoma (PAs) is unpredictable. Gene expression profiling has recently demonstrated an inverse relationship between myelin basic protein (MBP) expression and progression free survival (PFS) in PAs. We present here the pattern of expression of oligodendroglial differentiation markers (ODMs) in PAs by immunohistochemistry and their correlation with PI and PFS. Sixty-four cases of PA were reviewed and representative sections were stained for Ki-67 and ODMs, including MBP, platelet-derived growth factor receptor-alpha (PDGFR-alpha), Olig-1, and Olig-2. Sections were graded semi-quantitatively for intensity (I: 0-3+) and extent (E: 0-4+) of staining. PI was expressed as a percentage of Ki-67 positive cells. Immunoreactivity of MBP, PDGFR-alpha, Olig-1, and Olig-2 was observed in 84, 56, 97, and 75% of cases, respectively. There was a statistically significant inverse correlation between MBP expression and PI (r (2) = .696, p = .014). A positive correlation was observed between PDGFR-alpha and PI (r (2) = .727, p = .011). Further analysis showed a significant difference in PFS between low expressors [I + E score < or = 3] and high expressors (I + E score > or = 4) for PDGFR-alpha with p < .001. Notably, there was a significant difference in PFS between high expressors of MBP and high expressors of PDGFR-alpha with p < .001. These results suggest that expression of ODMs, especially MBP and PDGFR-alpha, may identify two clinical subsets of PA. In addition, we have shown the expression of 4 different ODMs in PAs, which may support the possibility that PAs arise from oligodendrocyte progenitor/precursor cells probably similar to the O2A progenitor cells in the mouse.

摘要

毛细胞型星形细胞瘤(PA)的生长模式不可预测。基因表达谱分析最近显示,PA中髓鞘碱性蛋白(MBP)表达与无进展生存期(PFS)呈负相关。我们在此通过免疫组织化学展示PA中少突胶质细胞分化标志物(ODM)的表达模式及其与增殖指数(PI)和PFS的相关性。回顾了64例PA病例,并对代表性切片进行Ki-67和ODM染色,包括MBP、血小板衍生生长因子受体α(PDGFR-α)、少突胶质细胞转录因子1(Olig-1)和少突胶质细胞转录因子2(Olig-2)。对切片染色的强度(I:0-3+)和范围(E:0-4+)进行半定量分级。PI以Ki-67阳性细胞的百分比表示。MBP、PDGFR-α、Olig-1和Olig-2的免疫反应性分别在84%、56%、97%和75%的病例中观察到。MBP表达与PI之间存在统计学显著负相关(r² = 0.696,p = 0.014)。PDGFR-α与PI之间观察到正相关(r² = 0.727,p = 0.011)。进一步分析显示,PDGFR-α低表达者[I + E评分≤3]与高表达者(I + E评分≥4)之间PFS存在显著差异,p < 0.001。值得注意的是,MBP高表达者与PDGFR-α高表达者之间PFS存在显著差异,p < 0.001。这些结果表明,ODM的表达,尤其是MBP和PDGFR-α,可能识别出PA的两个临床亚组。此外,我们展示了PA中4种不同ODM的表达,这可能支持PA起源于少突胶质细胞祖细胞/前体细胞的可能性,可能类似于小鼠中的O2A祖细胞。

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