Expression of pERK and pAKT in pediatric high grade astrocytomas: Correlation with YKL40 and prognostic significance
Expression of pERK and pAKT in pediatric high grade astrocytomas: Correlation with YKL40 and prognostic significance
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DOI：
10.1111/j.1440-1789.2011.01252.x
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发表时间：
2012-04-01
期刊：
影响因子：
2.3
通讯作者：
Giangaspero, Felice
中科院分区：
文献类型：
--
作者：
Antonelli, Manila;Massimino, Maura;Giangaspero, Felice
Ras信号通路由丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）和PI 3 K/AKT信号通路组成，是成人弥漫性胶质瘤中重要的致癌通路，但在儿童恶性胶质瘤中的研究较少。我们通过免疫组织化学方法研究了28例儿童高级别胶质瘤（WHO III级和IV级）中MAPK和AKT信号传导。我们寻求磷酸化ERK（p-ERK）和磷酸化AKT（p-AKT）与Ras通路中涉及的其他蛋白质（即YKL 40、表皮生长因子受体（EGFR）、EGFR vIII和c-Met）表达的可能关联。p-ERK和p-AKT的表达与预后相关。无c-Met和EGFR表达，仅1例EGFR vIII阳性。YKL-40蛋白表达率为43%。我们分别在61%和57%的儿童高级别胶质瘤中检测到p-ERK和p-AKT的表达。比较两组p-ERK和p-AKT高表达和低表达的统计学分析显示，p-AKT高表达患者的总体生存率有下降的趋势。ERK和AKT的激活表明这种蛋白在诱导儿童高级别胶质瘤中Ras信号通路的激活中可能起作用。此外，高水平的p-AKT与更差的总生存率相关。
The Ras signaling pathway, consisting of mitogen-activated protein kinase (MAPK) and PI3K/AKT signaling, is a prominent oncogenic pathways in adult diffuse gliomas, but few studies have evaluated such pathways in pediatric malignant gliomas. We investigated by immunohistochemistry MAPK and AKT signaling in a series of 28 pediatric high-grade gliomas (WHO grade III and IV). We sought a possible association of phospho-ERK (p-ERK) and phospho-AKT (p-AKT) with expression of other proteins involved in the Ras pathway, that is, YKL40, epidermal growth factor receptor (EGFR), EGFR vIII and c-Met. Moreover we correlated the expression of p-ERK and p-AKT with prognosis. No cases showed expression for c-Met and EGFR, and only one case was positive for EGFR vIII. YKL-40 protein was expressed in 43% of cases. We detected expression of p-ERK and p-AKT in 61% and 57%, respectively, of pediatric high grade gliomas. Statistical analysis comparing the two groups in term of high and low p-ERK and p-AKT expression showed a trend toward worse overall survival in patients with high expression of p-AKT. The activation of ERK and AKT suggest a possible role of this protein in inducing activation of the Ras signaling pathway in pediatric high-grade gliomas. Moreover high levels of p-AKT are associated with worse overall survival.