Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: Correlation with EGFR status, tumor grade, and survival
Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: Correlation with EGFR status, tumor grade, and survival
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DOI：
10.1097/01.jnen.0000248549.14962.b2
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发表时间：
2006-12-01
影响因子：
3.2
通讯作者：
Nutt, Catherine L.
中科院分区：
文献类型：
--
作者：
Mizoguchi, Masahiro;Betensky, Rebecca A.;Nutt, Catherine L.
弥漫性星形细胞胶质瘤是最常见的人类胶质瘤，其中胶质母细胞瘤是最恶性的形式。表皮生长因子受体 (EGFR) 基因扩增是胶质母细胞瘤中最常见的遗传变化之一，可导致各种下游信号分子的激活，包括 STAT3、MAPK 和 AKT。在本研究中，我们使用免疫组织化学方法研究了 82 例恶性星形细胞瘤（55 例胶质母细胞瘤和 27 例间变性星形细胞瘤）中这 3 种信号分子以及野生型 (EGFRwt) 和突变型 (EGFRvIII) EGFR 的激活状态。 EGFRwt（而非 EGFRvIII）免疫阳性的存在与胶质母细胞瘤中普遍存在的 EGFR 基因扩增显着相关。 STAT3 和 AKT 激活与 EGFR 状态显着相关，尽管 p-STAT3 的相关性仅归因于 EGFRvIII。这3种活化分子的分布随肿瘤级别的不同而显着变化；尽管间变性星形细胞瘤和胶质母细胞瘤之间 STAT3 的激活基本相同，但 MAPK 和 AKT 激活的增加似乎与间变性星形细胞瘤向胶质母细胞瘤的进展相关。最后，激活的 STAT3 和 AKT 分别可以略微预测预后的改善和恶化。总而言之，这些发现开始阐明体内星形细胞胶质瘤中这些信号传导途径之间的相互关系。
Diffuse astrocytic gliomas are the most common human glial tumors with glioblastoma being the most malignant form. Epidermal growth factor receptor (EGFR) gene amplification is one of the most common genetic changes in glioblastoma and can lead to the activation of various downstream signaling molecules, including STAT3, MAPK, and AKT. In this study, we investigated the activation status of these 3 signaling molecules as well as wild-type (EGFRwt) and mutant (EGFRvIII) EGFR in 82 malignant astrocytic gliomas (55 glioblastomas and 27 anaplastic astrocytomas) using immunohistochemistry. The presence of EGFRwt, but not EGFRvIII, immunopositivity correlated significantly with prevalent EGFR gene amplification in glioblastomas. STAT3 and AKT activation correlated significantly with EGFR status, although the correlation for p-STAT3 was attributed exclusively to EGFRvIII. The distribution of these 3 activated molecules varied significantly with tumor grade; although activation of STAT3 was essentially identical between anaplastic astrocytomas and glioblastomas, an increase in the activation of MAPK and AKT appeared to correlate with the progression of anaplastic astrocytoma to glioblastoma. Finally, activated STAT3 and AKT were marginally predictive of improved and worse prognosis, respectively. Taken together, these findings begin to elucidate the interrelationship between these signaling pathways in astrocytic gliomas in vivo.