Liang Muh-Lii, Ma Jing, Ho Michael, Solomon Lauren, Bouffet Eric, Rutka James T, Hawkins Cynthia
Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
J Neurooncol. 2008 May;87(3):247-53. doi: 10.1007/s11060-007-9513-1. Epub 2008 Jan 10.
The over-expression of several receptor tyrosine kinases in adult high grade astrocytomas (HGA) led to trials of tyrosine kinase inhibitors in these patients. Similar molecular genetic analysis of pediatric HGA is only beginning to be published. Thus it is unclear to what degree these pathways are also involved in the pediatric age group and whether they may also serve as useful therapeutic targets for children with HGAs. Here we investigated the protein expression profile of a series of pediatric HGAs. Following institutional ethical approval, clinical information and tumor samples were obtained for 42 HGA patients. Mean age at presentation was 10.1 years (range 0.13-19.3 years). OS was 12% and PFS was 3.7%. Extent of resection was associated with improved PFS (P = 0.0015) with a trend towards improved OS (P = 0.08). There was no significant effect of age or adjuvant therapy use on PFS or OS. Immunopositivity for each of the markers was as follows: p53 35%; PDGFR-alpha 45%; PDGFR-beta 31%; PTEN 67%; EGFR wild type 58%; EGFRvIII 2%. No significant effect on OS or PFS was found for any of the markers by log rank analysis. However, all long-term survivors expressed PTEN and were EGFRvIII negative. Further, there were distinct differences in protein expression between pediatric and adult HGAs suggesting that EGFR kinase inhibitors may not be beneficial for treatment of HGA in the pediatric age group and pointing to the need to study pediatric astrocytomas as distinct entities from adult astrocytomas.
几种受体酪氨酸激酶在成人高级别星形细胞瘤（HGA）中的过表达促使人们对这些患者进行酪氨酸激酶抑制剂试验。关于儿童HGA的类似分子遗传学分析才刚刚开始发表。因此，目前尚不清楚这些通路在儿童年龄组中的参与程度，以及它们是否也可作为儿童HGA患者有用的治疗靶点。在此，我们研究了一系列儿童HGA的蛋白质表达谱。在获得机构伦理批准后，我们获取了42例HGA患者的临床信息和肿瘤样本。就诊时的平均年龄为10.1岁（范围0.13 - 19.3岁）。总生存率为12%，无进展生存率为3.7%。切除范围与无进展生存率的改善相关（P = 0.0015），总生存率有改善趋势（P = 0.08）。年龄或辅助治疗的使用对无进展生存率或总生存率没有显著影响。各标志物的免疫阳性率如下：p53为35%；血小板衍生生长因子受体α（PDGFR-α）为45%；血小板衍生生长因子受体β（PDGFR-β）为31%；第10号染色体同源丢失性磷酸酶-张力蛋白（PTEN）为67%；表皮生长因子受体（EGFR）野生型为58%；EGFRvIII为2%。通过对数秩分析，未发现任何标志物对总生存率或无进展生存率有显著影响。然而，所有长期存活者均表达PTEN且为EGFRvIII阴性。此外，儿童和成人HGA之间在蛋白质表达上存在明显差异，这表明EGFR激酶抑制剂可能对儿童年龄组的HGA治疗无益，并指出有必要将儿童星形细胞瘤作为与成人星形细胞瘤不同的实体进行研究。
