Activation of the Hedgehog pathway in pilocytic astrocytomas.
Activation of the Hedgehog pathway in pilocytic astrocytomas.
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DOI：
10.1093/neuonc/noq026
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发表时间：
2010-08
期刊：
影响因子：
15.9
通讯作者：
Cooper MK
中科院分区：
文献类型：
--
作者：
Rush SZ;Abel TW;Valadez JG;Pearson M;Cooper MK
毛细胞型星形细胞瘤通常被认为是一种良性病变。然而，疾病发作在生命的头二十年最为普遍，儿童往往留下残留或复发的疾病和严重的发病率。Hedgehog（Hh）通路调节较高WHO级别胶质瘤的生长，在这项研究中，我们评估了这一调节通路在毛细胞型星形细胞瘤中的激活和运行状态。Hh通路转录靶点PTCH的表达水平在45%的分析的肿瘤标本（年龄1-22岁）中升高，并与患者年龄呈负相关。组织阵列的评价显示，少突胶质细胞瘤样特征、毛粘液样特征、浸润和坏死在年轻患者（患者中位年龄低于10岁）的标本中更常见。Hh通路组分PTCH和GLI 1以及增殖标记物Ki 67的免疫组织化学染色表明，10岁之前诊断的患者比10岁之后诊断的患者具有更高的染色指数。Ki 67与PTCH和GLI 1染色指数之间存在显著相关性，86%的Ki 67阳性细胞也表达PTCH。在原代细胞培养中证实了Hh途径的操作状态，并且可以以与配体依赖性机制一致的方式进行调节。总之，这些发现表明，Hh通路激活在儿童毛细胞星形细胞瘤中很常见，可能与诊断时年龄较小和肿瘤生长有关。
Pilocytic astrocytoma is commonly viewed as a benign lesion. However, disease onset is most prevalent in the first two decades of life, and children are often left with residual or recurrent disease and significant morbidity. The Hedgehog (Hh) pathway regulates the growth of higher WHO grade gliomas, and in this study, we have evaluated the activation and operational status of this regulatory pathway in pilocytic astrocytomas. Expression levels of the Hh pathway transcriptional target PTCH were elevated in 45% of tumor specimens analyzed (ages 1–22 years) and correlated inversely with patient age. Evaluation of a tissue array revealed oligodendroglioma-like features, pilomyxoid features, infiltration, and necrosis more commonly in specimens from younger patients (below the median patient age of 10 years). Immunohistochemical staining for the Hh pathway components PTCH and GLI1 and the proliferation marker Ki67 demonstrated that patients diagnosed before the age of 10 had higher staining indices than those diagnosed after the age of 10. A significant correlation between Ki67 and PTCH and GLI1 staining indices was measured, and 86% of Ki67-positive cells also expressed PTCH. The operational status of the Hh pathway was confirmed in primary cell culture and could be modulated in a manner consistent with a ligand-dependent mechanism. Taken together, these findings suggest that Hh pathway activation is common in pediatric pilocytic astrocytomas and may be associated with younger age at diagnosis and tumor growth.
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影响因子：
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