Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma
Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma
复制标题
DOI：
10.1215/15228517-2008-036
复制
发表时间：
2008-10-01
期刊：
影响因子：
15.9
通讯作者：
Grundy, Richard G.
中科院分区：
文献类型：
--
作者：
Ridley, Lee;Rahman, Ruman;Grundy, Richard G.
儿科室管膜瘤是一种神秘的肿瘤，其临床处理仍然是儿科肿瘤学中较难处理的问题之一。确定预后和治疗靶点的生物学相关性仍然是该病的一个重大挑战。因此，我们分析了一组潜在的生物标志物，以确定最佳的预后标志物。我们构建了74例患者(WHO II-III级)的97个颅内肿瘤的组织芯片，并用免疫组织化学方法分析了候选标志物核仁素、端粒酶催化亚单位(hTERT；抗体克隆44F12)、Survivin、Ki-67以及受体酪氨酸激酶I(RTK-I)家族的成员。端粒酶活性测定采用体外端粒重复序列扩增法，端粒长度测定采用端粒限制性片段分析法。核仁蛋白低表达和高表达的原发肿瘤的5年无事件生存率分别为74%+/-13%和31%+/-7%。多变量分析表明，低核仁素表达与较好的预后独立相关(风险比=6.25；95%可信区间1.6-24.2；p=0.008)。Ki-67和Survivin与组织学分级有关，但与预后无关。免疫组织化学检测RTK-I家族与肿瘤分级或预后无关。22例原发肿瘤中19例端粒酶活性明显，7例复发病例中5例端粒延长和/或维持。低核仁素表达是预测儿童脑室管膜瘤预后的唯一最重要的生物学指标。此外，对于儿童室管膜瘤，端粒酶的重新激活和端粒重复序列的维持似乎是必要的。进步。这些发现需要在临床试验环境中得到证实。神经肿瘤学10,675-689,2008(发表于神经肿瘤学[连载在线]，DOC.2008年08月13日07-00243。网址http://neuro-oncology.dukejournals.org；DOI：10.1215/15228517-10.1215-036)
Pediatric ependymomas are enigmatic tumors, and their clinical management remains one of the more difficult in pediatric oncology. The identification of biological correlates of outcome and therapeutic targets remains a significant challenge in this disease. We therefore analyzed a panel of potential biological markers to determine optimal prognostic markers. We constructed a tissue microarray from 97 intracranial tumors from 74 patients (WHO grade II-III) and analyzed the candidate markers nucleolin, telomerase catalytic subunit (hTERT; antibody clone 44F12), survivin, Ki-67, and members of the receptor tyrosine kinase I (RTK-I) family by immunohistochemistry. Telomerase activity was determined using the in vitro-based telomere repeat amplification protocol assay, and telomere length was measured using the telomere restriction fragment assay. Primary tumors with low versus high nucleolin protein expression had a 5-year event-free survival of 74% +/- 13% and 31% +/- 7%, respectively. Multivariate analysis identified low nucleolin expression to be independently associated with a more favorable prognosis (hazard ratio = 6.25; 95% confidence interval, 1.6-24.2; p = 0.008). Ki-67 and survivin correlated with histological grade but not with outcome. Immunohistochemical detection of the RTK-I family did not correlate with grade or outcome. Telomerase activity was evident in 19 of 22 primary tumors, with telomere lengthening and/or maintenance occurring in five of seven recurrent cases. Low nucleolin expression was the single most important biological predictor of outcome in pediatric intracranial ependymoma. Furthermore, telomerase reactivation and maintenance of telomeric repeats appear necessary for childhood ependymoma. progression. These findings require corroboration in a clinical trial setting. Neuro-Oncology 10, 675-689, 2008 (Posted to Neuro-Oncology [serial online], Doc. 07-00243, August 13, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-036)