Expression of p53, EGFR, pRb and bcl-2 proteins in pediatric glioblastoma multiforme: A study of 54 patients

Expression of p53, EGFR, pRb and bcl-2 proteins in pediatric glioblastoma multiforme: A study of 54 patients
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DOI:
10.1159/000088731
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发表时间:
2005-01-01
影响因子:
0.7
通讯作者:
Kolluri, VRS
Kolluri, VRS
中科院分区:
医学4区
文献类型:
--
作者:
Ganigi, PM;Santosh, V;Kolluri, VRS

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儿童多形性胶质母细胞瘤 (GBM) 肿瘤已被确定为“从头”肿瘤,已知在生物学、遗传学和患者的最终生存方面与成人肿瘤不同。为了评价肿瘤生物学标志物在完善预后评估中的效用,我们回顾性分析了1995年至2001年间在我院手术的54例发生在大脑不同解剖部位的儿童GBM(年龄范围9个月至15岁)。通过免疫组织化学分析p53、表皮生长因子受体(EGFR)、bcl-2和视网膜母细胞瘤蛋白(pRb)的表达,结果为与临床特征、MIB-1标记指数(LI)和患者生存率进行比较。 53.7% 的病例出现 p53 免疫反应性,主要发生在丘脑 (75%) 和脑叶 (62.2%),其次是脑干肿瘤 (30%)。小脑肿瘤中不存在这种情况。与 p53 阴性肿瘤相比,p53 阳性肿瘤具有更高的 MIB-1 LI (p = 0.003)。 EGFR 和 bcl-2 过度表达分别在 25.9% 和 33.3% 的病例中观察到,pRb 表达缺失仅在 7.4% 的病例中明显,表明该基因功能的缺失与儿童 GBM 没有显着相关。 p53 和 bcl-2 表达在预后较差的患者中最为明显。我们的结果表明 p53 表达状态在大量儿科幕上肿瘤中被发现。 bcl-2 过度表达的 p53 通常与不祥的预后相关。进一步的分子表征将为这些肿瘤的生物学提供新的见解,并为未来的治疗决策奠定基础。版权所有 (c) 2005 S. Karger AG,巴塞尔。
Pediatric glioblastoma multiforme ( GBM) tumors, which have been established as 'de novo' neoplasms, are known to differ from their adult counterparts in terms of biology, genetics and ultimately survival of patients. In order to evaluate the utility of markers of tumor biology for refining prognostic assessment, we retrospectively analyzed 54 pediatric GBMs ( age range 9 months to 15 years) occurring at different anatomical sites in the brain, operated at our institute between 1995 and 2001. The expression of p53, epidermal growth factor receptor ( EGFR), bcl-2 and retinoblastoma proteins ( pRb) was analyzed by immunohistochemistry and the results were compared with the clinical profile, MIB-1 labeling index ( LI) and patient survival. p53 immunoreactivity was noted in 53.7% of cases, predominantly in thalamic ( 75%) and cerebral lobar ( 62.2%), followed by brainstem tumors ( 30%). It was absent in cerebellar tumors. p53-positive tumors had a higher MIB-1 LI, compared to p53-negative tumors ( p = 0.003). EGFR and bcl-2 overexpression was observed in 25.9% and 33.3% of cases, respectively, and loss of pRb expression was evident in only 7.4% of cases, indicating that loss of this gene function is not significantly involved in pediatric GBMs. p53 and bcl-2 expression were maximally noted in patients with poorer outcome. Our results indicate that p53 expression status is noted in a significant number of pediatric supratentorial neoplasms. p53 with bcl-2 overexpression is more often associated with ominous prognosis. Further molecular characterization would provide newer insights into the biology of these neoplasms and form a basis for future therapeutic decision making. Copyright (c) 2005 S. Karger AG, Basel.