Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes
Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes
复制标题
DOI：
10.1111/j.1750-3639.1998.tb00191.x
复制
发表时间：
1998-10-01
期刊：
影响因子：
6.4
通讯作者：
Miller, DC
中科院分区：
文献类型：
--
作者：
Newcomb, EW;Cohen, H;Miller, DC
一种或多种生长控制基因（包括p16、p53、EGF受体（EGFR）、MDM2或Bcl-2）的表达失调可能导致GEM的耐药表型和通常较差的患者生存率。临床上，GEM被分为两大类，定义为(1)低级别肿瘤的组织学进展（“进行性”或“继发性”GEM）与(2)没有既往病史的初始临床表现（“新生”或“原发性”GEM）。利用p53基因突变的分子遗传学分析和EGFR过表达的免疫表型分析，可以区分多达四种GEM变异，包括p53(+)/EGFR（+）进行性变异或p53/EGFR（+）新生变异。我们检查了80名被诊断为星形细胞性GEM的成年患者的生存率，按年龄类别（bb0 40岁，41-60岁或61-80岁）进行分层，以确定任何一种给定生长控制基因的改变或GEM的不同遗传变异（进行性与新生性）是否与不同的生存结果相关。MDM2或Bcl-2在不同年龄组或基因表达方面无显著差异，表明GEM缺乏预后价值。此外，GEM患者的临床结果显示，任何GEM变异（包括进行性和新生GEM变异，尽管基因型不同，但生物学行为相似）在每个年龄类别中均无显著差异。通过两两比较，三分之一p16表达正常的GEM患者显示MDM2蛋白积累，使用Bonferroni程序，这种关联接近统计学意义（0.01 < P < 0.05）。这些GEM可能代表一种变体，其中p19(ARF)/MDM2/p53通路可能失调，而不是p16/cyclin D-CDK4/Rb通路。
Deregulated expression of one or more growth control genes including p16, p53, EGF receptor (EGFR), MDM2 or Bcl-2 may contribute to the treatment resistance phenotype of GEM and generally poor patient survival, Clinically, GEM have been divided into two major groups defined by (1) histologic progression from a low grade tumor ("progressive" or "secondary" GEM) contrasted with (2) those which show initial clinical presentation without a prior history ("de novo" or "primary" GEM). Using molecular genetic analysis for p53 gene mutations together with immunophenotyping for overexpression of EGFR, up to four GEM variants can be distinguished, including the p53(+)/EGFR(+) progressive or the p53/EGFR(+) de novo variant. We examined the survival of 80 adult patients diagnosed with astrocytic GEM stratified by age category (>40, 41-60 or 61-80) to determine whether alterations in any one given growth control gene or whether different genetic variants of GEM (progressive verses de novo) were associated with different survival outcomes, Survival testing using Kaplan-Meier plots for GBM patients with or without altered expression of p16, p53, EGFR, MDM2 or Bcl-2 showed no significant differences by age group or by gene expression indicating a lack of prognostic value for GEM. Also the clinical outcome among patients with GEM showed no significant differences within each age category for any GEM variant including the progressive and de novo GEM variants indicating similar biologic behavior despite different genotypes, Using a pairwise comparison, one-third of the GEM with normal p16 expression showed accumulation of MDM2 protein and this association approached statistical significance (0.01 < P < 0.05) using the Bonferroni procedure. These GEM may represent a variant in which the p19(ARF)/MDM2/p53 pathway may be deregulated rather than the p16/cyclin D-CDK4/Rb pathway.