胶质母细胞瘤患者的 IDH1、ATRX、p53 和 Ki67 表达:其临床和预后意义--一项前瞻性研究

Asian journal of neurosurgery Pub Date : 2024-03-26 eCollection Date: 2024-03-01 DOI:10.1055/s-0042-1750783
Mukta Meel, Arpita Jindal, Mukesh Kumar, Kusum Mathur, Ashok Singh
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引用次数: 0

摘要

背景 多形性胶质母细胞瘤(GBM)是一种恶性侵袭性原发性脑肿瘤,预后不良。这种不良预后是由于持续存在的 GBM 细胞具有高度侵袭性,它们会主动从主要瘤体逃逸到周围的正常脑组织中,从而导致肿瘤的发展和复发。根据生物标志物图解,可将其分为分子亚组。目的 (1) 通过免疫组化确定一组 GBM 中 IDH1、ATRX、p53 和 Ki67 的表达。(2)确定这些生长控制基因在 GBM 中的蛋白表达变化是否与患者生存有关。(3)不论组织病理学诊断结果如何,建立预后不同的 GBM 分子亚群。结果 在这项前瞻性观察研究中,共纳入了 35 例经组织学诊断的胶质母细胞瘤病例。发病时的平均年龄为(43.46 ± 17.25)岁,男女比例为 1.3:1。在 35 例病例中,23 例出现微血管增生。10例出现大面积坏死灶(>50%),27例有丝分裂计数≥5/高倍视野(HPF)。35 例病例中,5 例(14.3%)显示 IDH1 免疫阳性,30 例(85.7%)IDH1 阴性。24例(68.6%)保留了ATRX,11例(31.4%)丢失了ATRX。31例(88.6%)病例中出现了p53免疫表达,而4例(11.4%)病例中p53呈阴性。总体中位生存期(OS)为 6 个月。在两对蛋白中,三种组成分别为IDH1-/p53+(74.3%)、ATRX +/IDH1-(62.9%)和ATRX +/p53+(57.1%)。三蛋白免疫组化联合分析显示了五种不同的分子变异。此外,8.6%(3/35)的样本三种蛋白表达均异常,即 ATRX-/p53 +/IDH1 +,而 11.4%(4/35)的样本为野生型蛋白表达组,即 ATRX +/p53-/IDH1-。结论 在单蛋白表达的患者中,Kaplan-Meier生存率分析表明,IDH1突变型胶质母细胞瘤的OS在统计学上更好。在双蛋白配对的病例中,IDH1/p53与较好的中位生存期有显著的统计学关联。对IDH1/ATRX/p53蛋白组合患者的生存率分析也表明,其OS更佳。因此,可以利用这些蛋白表达特征以及组合蛋白表达特征将 GBM 划分为与预后相关的亚组。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IDH1, ATRX, p53, and Ki67 Expression in Glioblastoma patients: Their Clinical and Prognostic Significance-A Prospective Study.

Context  Glioblastoma multiforme (GBM) is a malignant and aggressive primary brain tumor with a poor prognosis. This adverse prognosis is due to the tumor's tendency for advancement and recurrence caused by highly intrusive nature of the persisting GBM cells that actively escape from the main tumor mass into the surrounding normal brain tissue. On the basis of biomarker illustration, it can be classified into molecular subgroups. Aims  (1) To determine the expression of IDH1, ATRX, p53, and Ki67 by immunohistochemistry, in a cohort of GBMs. (2) To determine whether altered protein expression of any of these growth-control genes in GBM will show association with patient survival. (3) To establish prognostically distinct molecular subgroups of GBM, irrespective of histopathological diagnosis. Results  In this prospective observational study, 35 histologically diagnosed cases of glioblastoma were enrolled. The mean age at the time of presentation was 43.46 ± 17.25 years with a male:female ratio of 1.3:1. Of the 35 cases, microvascular proliferation was seen in 23 cases. Large foci of necrosis (>50%) were seen in 10 cases and 27 cases had mitotic count ≥ 5/high power field (HPF). Of 35 cases, 5 (14.3%) cases showed IDH1 immunopositivity and 30 (85.7%) cases were negative for IDH1. ATRX was retained in 24 (68.6%) cases, while it was lost in 11 (31.4%) cases. The p53 immunoexpression was seen in 31 (88.6%) cases, whereas p53 was negative in 4 (11.4%) cases. The overall median survival (OS) was 6 months. In two protein pairs, the three compositions were IDH1-/p53+ (74.3%), ATRX +/IDH1- (62.9%), and ATRX +/p53+ (57.1%). Combined three-protein immunohistochemical analysis revealed five different molecular variants. Also, 8.6% (3/35) of the samples had aberrant protein expression of all three proteins, i.e., ATRX-/p53 +/IDH1 + , while 11.4% (4/35) were wild-type protein expression group, i.e., ATRX +/p53-/IDH1-. Conclusion  In patients with single protein expression, Kaplan-Meier survival analysis showed statistically better OS in IDH1 mutant glioblastomas. In cases with double protein pairs, IDH1/p53 revealed statistically significant association with better median OS. The survival analysis of patients with IDH1/ATRX/p53 protein combinations also denoted a better OS. Hence, GBM can be grouped into prognostically relevant subgroups using these protein expression signatures individually, as well as the combined protein expression signatures.

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