MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor.
MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor.
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神经胶质瘤中的MDM2和p53表达：多元生存分析，包括增殖标记和表皮生长因子受体。
DOI：
10.1038/bjc.1997.216
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发表时间：
1997
影响因子：
8.8
通讯作者：
Thomas-Tsagli E
中科院分区：
文献类型：
--
作者：
Korkolopoulou P;Christodoulou P;Kouzelis K;Hadjiyannakis M;Priftis A;Stamoulis G;Seretis A;Thomas-Tsagli E
在61例中枢神经系统胶质瘤患者（53例星形细胞瘤和8例少突胶质细胞瘤）的石蜡包埋组织中评价了p53和小鼠双微体2（MDM 2）癌蛋白表达，并与增殖相关标志物[即增殖细胞核抗原（PCNA）、Ki-67和核组织区（NORs）]和表皮生长因子受体（EGFR）相关。应用单克隆抗体PC-10、MIB-1、DO-1、1B_（10）和EGFR_（113）及胶体银硝酸盐（AgNOR）技术。MDM 2和p53在28%的病例中共表达。在15%的病例中观察到p53阳性/MDM 2阴性表型，在20%的病例中观察到p53阴性/MDM 2阳性表型。p53、MDM 2表达与肿瘤分级、增殖指数呈正相关。弥漫性星形细胞瘤组单因素分析显示，年龄大、组织学分级高、PCNA标记指数（LI）高、AgNOR评分高与总生存率降低有关（P < 0.05）。p53 LI、Ki-67 LI、AgNOR评分、肿瘤部位和分级影响无病生存率（P < 0.05），而影响复发后生存率的仅有组织学分级和Ki-67 LI（P < 0.1）。多因素分析显示，年龄、放疗、PCNA LI和p53 LI是影响总生存率的独立因素。p53 LI、Ki-67 LI、MDM 2 LI、EGFR LI、分级和治疗类型是无病生存期的独立预测因子，而分级是复发后生存期的唯一独立预测因子。我们的研究结果表明，p53 LI和MDM 2 LI，EGFR表达以及增殖标记物（PCNA和Ki-67）是弥漫性星形细胞瘤患者的总生存期和无病生存期的有用指标。
p53 and the murine double minute 2 (MDM2) oncoprotein expression was evaluated in paraffin-embedded tissue from 61 patients with central nervous system gliomas (53 astrocytomas and eight oligodendrogliomas) and related to proliferation-associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and nuclear organizer regions (NORs)] and epidermal growth factor receptor (EGFR). We used the monoclonal antibodies PC-10, MIB-1, DO-1, 1B1O and EGFR 113 and the colloid silver nitrate (AgNOR) technique. MDM2 and p53 were co-expressed in 28% of cases. A p53-positive/MDM2-negative phenotype was observed in 15% and a p53-negative/MDM2-positive phenotype in 20% of cases. There was a positive correlation of p53 and MDM2 expression with grade and proliferation indices. Univariate analysis in the group of diffuse astrocytomas showed that older age, high histological grade, high PCNA labelling index (LI) and high AgNOR score were associated with reduced overall survival (P < 0.05). p53 LI, Ki-67 LI, AgNOR score, tumour location and grade influenced disease-free survival (P < 0.05), whereas the only parameters affecting post-relapse survival were histological grade and Ki-67 LI (P < 0.1). Multivariate analysis revealed that age, radiotherapy, PCNA LI and p53 LI were the independent predictors of overall survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were independent predictors of disease-free survival, and grade was the only independent predictor of post-relapse survival. Our results indicate that p53 LI and MDM2 LI, EGFR expression as well as proliferation markers (PCNA and Ki-67) are useful indicators of overall and disease-free survival in diffuse astrocytoma patients.