Glioblastoma Patients Epidermal Growth Factor Receptor , and Survival in Analysis of Complex Relationships between Age , p 53 , Updated
Glioblastoma Patients Epidermal Growth Factor Receptor , and Survival in Analysis of Complex Relationships between Age , p 53 , Updated
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发表时间：
2001
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通讯作者：
Martha L. Simmons;K. Lamborn;M. Takahashi;Pengchin Chen;M. Israel;M. S. Berger;T. Godfrey;J. Nigro;M. Prados;Susan M. Chang;Fredrick G. Barker;K. Aldape
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作者：
Martha L. Simmons;K. Lamborn;M. Takahashi;Pengchin Chen;M. Israel;M. S. Berger;T. Godfrey;J. Nigro;M. Prados;Susan M. Chang;Fredrick G. Barker;K. Aldape
多形性胶质母细胞瘤（GBM）预后不佳。然而，存在一系列的生存时间，定义预后组的参数可能有助于优化治疗。为了确定这样的预后组，我们分析了来自两个临床方案的110例新诊断的GBM的肿瘤组织。与其他研究相似，我们发现表皮生长因子受体（EGFR）过表达（通过免疫组化评估）、p53免疫阳性或p53突变与整个样本的生存率无关。然而，EGFR过表达在小于中位年龄的患者中显示出预后较差的趋势，但在大于中位年龄的患者中预后较好。EGFR与年龄组的这种相互作用具有统计学显著性，并使我们将进一步分析的重点放在年轻患者上。在该组中，EGFR过表达与较差的生存率之间的统计学显著相关性在p53阴性而非p53阳性肿瘤中被确定。我们发现了一个类似的结果后，这些案件的突变p53：EGFR过度表达与生存呈负相关，只有在p53野生型病例。为了证实这一意外结果，在相同的两个临床方案中，在来自年轻患者的另外42个肿瘤的验证样本中重现了这一发现。年轻患者中EGFR和p53之间的复杂关系仍然存在于多变量分析中，该分析纳入了其他预后变量。结果表明，GBM预后标志物的分析是复杂的，最大的信息可能需要基于年龄和特定标志物（如p53）的状态进行亚组分析。此外，他们还提出了一个特定的患者群体，重点关注有希望的靶向EGFR的治疗。
Glioblastoma multiforme (GBM) carries a dismal prognosis. However, a range of survival times exists, and parameters that define prognostic groups may help to optimize treatment. To identify such prognostic groups, we analyzed tumor tissue from 110 cases of newly diagnosed GBM from two clinical protocols. Similar to other studies, we found no association of epidermal growth factor receptor (EGFR) overexpression (as assessed by immunohistochemistry), p53 immunopositivity, or p53 mutation with survival in the entire sample. However, EGFR overexpression showed trends toward worse prognosis in patients younger than the median age, but better prognosis in patients older than the median age. This interaction of EGFR with age group was statistically significant and led us to focus our further analyses on the younger patients. In this group, a statistically significant association of EGFR overexpression with worse survival was identified in the p53-negative but not p53-positive tumors. We found a similar result after screening these cases for mutations in p53: EGFR overexpression was negatively associated with survival only in the p53 wild-type cases. To confirm this unexpected result, this finding was reproduced in a validation sample of an additional 42 tumors from younger patients on the same two clinical protocols. This complex relationship between EGFR and p53 in younger patients remained in a multivariate analysis that incorporated additional prognostic variables. The results suggest that analysis of prognostic markers in GBM is complex, and maximal information may require analysis of subgroups based on age and the status of specific markers such as p53. In addition, they suggest a specific group of patients on which to focus promising therapies targeting EGFR.