异柠檬酸脱氢酶(IDH)突变、1p/19q 缺失及磷酸酶和张力蛋白同源物(PTEN)缺失分析可明确临床低级别弥漫性胶质瘤的预后。
Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas.
作者信息
Sabha Nesrin, Knobbe Christiane B, Maganti Majula, Al Omar Soha, Bernstein Mark, Cairns Rob, Çako Besmira, von Deimling Andreas, Capper David, Mak Tak W, Kiehl Tim-Rasmus, Carvalho Philippe, Garrett Evelyn, Perry Arie, Zadeh Gelareh, Guha Abhijit
出版信息
Neuro Oncol. 2014 Jul;16(7):914-23. doi: 10.1093/neuonc/not299.
BACKGROUND
Grades II and III gliomas have unpredictable rates of progression, making management decisions difficult. Currently, several clinical and radiological characteristics are utilized to predict progression and survival but collectively are suboptimal.
METHODS
In this study, we analyzed a set of 108 nonenhancing hemispheric grade II-III gliomas. Demographic variables, including patient age, tumor diameter, extent of resection, and performance status, were combined with molecular data (IDH mutation status [mIDH], 1p/19q codeletion, PTEN deletion, and EGFR amplification). A complete dataset for all variables was compiled for 70 of the 108 patients. Both univariable and multivariable analyses were performed to determine whether the molecular data singly or in combination offer advantages over tumor type and grade for prediction of overall survival (OS) and/or progression-free rate (PFR).
RESULTS
Patient age, clinical variables (tumor diameter, extent of resection, performance status), and pathology (tumor type and grade) were not predictive of OS or PFR. IDH mutation status alone was predictive of longer OS and PFR for the entire group of tumors; 1p/19q deletion alone was predictive of OS but not PFR. In the multivariable analysis, none of the clinical or demographic factors were predictive of OS or PFR. IDH mutation status, 1p/19q codeletion, and PTEN deletion were predictive of OS (P = .003, P = .005, P = .02, respectively). Both mIDH (P < .001) and the interaction term of 1p/19q and PTEN (P < .001) were found to be predictive of PFR.
CONCLUSIONS
We conclude that the combination of mIDH, 1p/19q codeletion, and PTEN deletion may be particularly effective in discriminating good prognosis from poor prognosis hemispheric gliomas. We propose that such a scheme merits testing on larger prospective cohorts. Should our findings be confirmed, routine clinical analysis of hemispheric gliomas for mIDH, 1p/19q codeletion, and PTEN deletion would be justified.
背景
II级和III级胶质瘤的进展速度难以预测,这使得治疗决策变得困难。目前,有几个临床和放射学特征被用于预测进展和生存情况,但总体而言效果欠佳。
方法
在本研究中,我们分析了一组108例非强化半球型II-III级胶质瘤。将人口统计学变量,包括患者年龄、肿瘤直径、切除范围和功能状态,与分子数据(异柠檬酸脱氢酶突变状态 [mIDH]、1p/19q共缺失、PTEN缺失和表皮生长因子受体扩增)相结合。为108例患者中的70例编制了所有变量的完整数据集。进行了单变量和多变量分析,以确定分子数据单独或联合使用在预测总生存期(OS)和/或无进展率(PFR)方面是否比肿瘤类型和分级更具优势。
结果
患者年龄、临床变量(肿瘤直径、切除范围、功能状态)和病理(肿瘤类型和分级)均不能预测OS或PFR。仅IDH突变状态可预测整个肿瘤组更长的OS和PFR;仅1p/19q缺失可预测OS,但不能预测PFR。在多变量分析中,没有任何临床或人口统计学因素可预测OS或PFR。IDH突变状态、1p/19q共缺失和PTEN缺失可预测OS(分别为P = 0.003、P = 0.005、P = 0.02)。发现mIDH(P < 0.001)以及1p/19q和PTEN的交互项(P < 0.001)均可预测PFR。
结论
我们得出结论,mIDH、1p/19q共缺失和PTEN缺失的联合使用在区分半球型胶质瘤的预后好坏方面可能特别有效。我们建议这样的方案值得在更大的前瞻性队列中进行测试。如果我们的发现得到证实,对半球型胶质瘤进行mIDH、1p/19q共缺失和PTEN缺失的常规临床分析将是合理的。
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