Kyritsis A P, Bondy M L, Hess K R, Cunningham J E, Zhu D, Amos C J, Yung W K, Levin V A, Bruner J M
Departments of Neuro-Oncology, Biomathematics, Epidemiology, and Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 1995 Dec;1(12):1617-22.
Abnormal p53 as revealed by immunostaining has been shown to be a predictor of poor outcome in a variety of malignant tumors. This study examines the relationship of p53 immunostaining and survival in 182 adult patients with gliomas. Tumor tissues obtained from patients with glioma within 4 months of initial diagnosis were investigated by immunohistochemical analysis for detection of p53 protein abnormalities using the monoclonal antibody PAb 1801. There were 122 patients with glioblastoma multiforme, 48 patients with anaplastic glioma, and 12 patients with low-grade glioma. Among these patients, 73 of those with glioblastoma multiforme, 35 with anaplastic glioma, and 6 with low-grade glioma had positive p53 immunoreactivity. Kaplan-Meier survival plots (log rank test) showed that the patients with anaplastic astrocytoma or low-grade glioma and p53-positive tumors had longer survival times compared to the patients with p53-negative tumors. No differences in survival were detected among the glioblastoma patients. Cox proportional hazards regression analysis, adjusted for age at diagnosis, showed that the p53 positivity was a significant predictor of longer survival (relative risk = 0.56; 95% confidence intervals = 0.35, 0.90; P = 0. 015) in anaplastic astrocytoma patients, but not in glioblastoma patients (relative risk = 1.03; 95% confidence intervals = 0.82, 1. 29; P = 0.80). These results suggest that anaplastic glioma patients with p53 protein alterations may have a better response to chemoradiation, possibly because the malignant cells cannot arrest in G1 to correct lethal damage induced by chemotherapy or radiotherapy.
免疫染色显示的异常p53已被证明是多种恶性肿瘤预后不良的一个预测指标。本研究调查了182例成年胶质瘤患者中p53免疫染色与生存情况的关系。对初次诊断后4个月内从胶质瘤患者获取的肿瘤组织进行免疫组织化学分析，使用单克隆抗体PAb 1801检测p53蛋白异常情况。其中有122例多形性胶质母细胞瘤患者、48例间变性胶质瘤患者和12例低级别胶质瘤患者。在这些患者中，多形性胶质母细胞瘤患者有73例、间变性胶质瘤患者有35例、低级别胶质瘤患者有6例p53免疫反应呈阳性。Kaplan-Meier生存曲线（对数秩检验）显示，间变性星形细胞瘤或低级别胶质瘤且p53阳性肿瘤的患者比p53阴性肿瘤的患者生存时间更长。在胶质母细胞瘤患者中未检测到生存差异。经诊断时年龄校正的Cox比例风险回归分析显示，p53阳性是间变性星形细胞瘤患者更长生存时间的一个显著预测指标（相对风险=0.56；95%置信区间=0.35，0.90；P=0.015），但在胶质母细胞瘤患者中并非如此（相对风险=1.03；95%置信区间=0.82，1.29；P=0.80）。这些结果表明，p53蛋白改变的间变性胶质瘤患者可能对放化疗有更好的反应，可能是因为恶性细胞无法在G1期停滞以纠正化疗或放疗诱导的致命损伤。
