Ständer Marko, Peraud Aurelia, Leroch Barbara, Kreth Friedrich W
Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
Cancer. 2004 Sep 1;101(5):1028-35. doi: 10.1002/cncr.20432.
The goal of the current study was to retrospectively assess the prognostic impact of TP53 mutation status and P53 expression/accumulation on long-term outcome for adult patients with supratentorial World Health Organization (WHO) Grade II astrocytoma or oligoastrocytoma.
The authors revisited a previously published short-term data set containing information on 159 consecutive patients who were treated between 1991 and 1998. Each patient was screened for TP53 mutations and P53 overexpression/accumulation. The reference point for all analyses was the date of surgical treatment, and the date of last follow-up examination was August 2002. Overall survival, progression-free survival, postrecurrence survival, and time to malignant transformation were estimated using the Kaplan-Meier method, and potential prognostic factors were evaluated using the multivariate proportional hazards model.
The median follow-up duration for survivors was 80.4 months (standard deviation, 33.0 months). TP53 mutations, which were present in 49.1% of all tumors, occurred preferentially in gemistocytic tumors (P < 0.05). In addition, the TP53 status of the primary tumor was predictive of the TP53 status of the recurrent tumor in all cases of disease recurrence. The 5-year overall and progression-free survival rates were 77.5% and 43.2%, respectively, and the risk of malignant transformation at 5 years postsurgery was 32.7%. Unfavorable prognostic factors with respect to survival duration included older age (> or = 50 years; P < 0.002), gemistocytic subtype (P < 0.01), and positive TP53 mutation status (P < 0.05), all of which were also negatively associated with progression-free survival (P < 0.05, P < 0.001, and P < 0.003, respectively). In contrast, positive TP53 mutation status was the only significant predictor of a reduction in time to malignant transformation (P < 0.03). P53 overexpression/accumulation did not exhibit prognostic relevance in any of the multivariate models constructed in the current study.
TP53 mutations are common early events in the pathogenesis of WHO Grade II astrocytoma or oligoastrocytoma. In the current study, positive TP53 mutation status (but not P53 overexpression/accumulation) was found to be an independent unfavorable predictor of survival, progression-free survival, and time to malignant transformation. The therapeutic implications of these findings have yet to be determined.
本研究的目的是回顾性评估TP53突变状态和P53表达/积累对幕上世界卫生组织（WHO）II级星形细胞瘤或少突星形细胞瘤成年患者长期预后的影响。
作者重新审视了一个先前发表的短期数据集，其中包含1991年至1998年间接受治疗的159例连续患者的信息。对每位患者进行TP53突变和P53过表达/积累的筛查。所有分析的参考点为手术治疗日期，最后一次随访检查日期为2002年8月。采用Kaplan-Meier方法估计总生存期、无进展生存期、复发后生存期和恶性转化时间，并使用多变量比例风险模型评估潜在的预后因素。
幸存者的中位随访时间为80.4个月（标准差，33.0个月）。TP53突变存在于所有肿瘤的49.1%中，在肥胖细胞型肿瘤中更常见（P < 0.05）。此外，在所有疾病复发病例中，原发肿瘤的TP53状态可预测复发肿瘤的TP53状态。5年总生存率和无进展生存率分别为77.5%和43.2%，术后5年恶性转化风险为32.7%。与生存时间相关的不良预后因素包括年龄较大（≥50岁；P < 0.002）、肥胖细胞型亚型（P < 0.01）和TP53突变状态阳性（P < 0.05），所有这些因素也与无进展生存期呈负相关（分别为P < 0.05、P < 0.001和P < 0.003）。相比之下，TP53突变状态阳性是恶性转化时间缩短的唯一显著预测因素（P < 0.03）。在本研究构建的任何多变量模型中，P53过表达/积累均未显示出预后相关性。
TP53突变是WHO II级星形细胞瘤或少突星形细胞瘤发病机制中常见的早期事件。在本研究中，TP53突变状态阳性（而非P53过表达/积累）被发现是生存、无进展生存期和恶性转化时间的独立不良预测因素。这些发现的治疗意义尚待确定。
