低度和高度胶质瘤中的同基因CDKN2A/B缺失:个体患者数据和p16免疫组化检测预测值的荟萃分析。

IF 6.2 2区 医学 Q1 NEUROSCIENCES
Darius Noack, Johannes Wach, Alonso Barrantes-Freer, Nils H Nicolay, Erdem Güresir, Clemens Seidel
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引用次数: 0

摘要

CDKN2A/B缺失与低级别和高级别胶质瘤的预后相关。这方面的数据来自不同的系列,目前尚缺乏对同源 CDKN2A/B 缺失的生存风险的准确估计。除基因检测外,p16免疫组化(IHC)作为一种成本较低的间接检测CDKN2A/B改变的方法也是可行的,但尚未在更大的数据集中得到验证。本荟萃分析旨在:(1)重建患者个体数据(IPD),并根据所有文献中的 CDKN2A/B 状态分层估算总生存期(OS);(2)确定已发表研究中用于 CDKNA2/B 检测的 p16 检测的准确性。为了根据 CDKN2A/B 状态进行生存率分析,我们筛选了 460 条记录,纳入了 4 篇文章,共 714 名参与者。在IDH-野生型(IDH-wt)胶质瘤中,57.07%的患者存在缺失,而在IDH-突变型(IDH-mut)胶质瘤中,只有9.76%的患者存在缺失。IDH-wt胶质瘤和同源CDKN2A/B缺失患者的中位OS为13.0个月,而CDKN2A/B未缺失患者的中位OS为18.0个月(P = 0.014,Log-Rank)。CDKN2A/B 基因同源缺失患者的死亡风险增加了 1.5(95%-CI 1.1-2.1)。未发生CDKN2A/B缺失的IDH突变胶质瘤患者的中位生存期为92.0个月,而发生CDKN2A/B缺失的患者的中位生存期为40.0个月(P为5%,在IDH突变胶质瘤中为5%)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing.

CDKN2A/B deletions are prognostically relevant in low- and high-grade gliomas. Data on this is derived from heterogeneous series, an accurate estimation of survival risk from homozygous CDKN2A/B deletion is missing. Besides genetic testing, p16-immunohistochemistry (IHC) as a less cost intensive means for indirect detection of CDKN2A/B alterations is possible but not validated in larger datasets. The present meta-analysis aimed to (1) reconstruct individual patient data (IPD) and estimate overall survival (OS) stratified by CDKN2A/B status from all literature and to (2) determine accuracy of p16 testing for CDKNA2/B detection from published studies. For survival analysis according to CDKN2A/B status 460 records were screened, four articles with 714 participants were included. In IDH-wildtype (IDH-wt) gliomas, 57.07% harbored the deletion compared to 9.76% in IDH-mutant (IDH-mut) gliomas. Median OS of patients with IDH-wt gliomas and homozygous CDKN2A/B deletion was 13.0 months compared to 18.0 months with non-deleted CDKN2A/B (p = 0.014, Log-Rank). With homozygous deletion of CDKN2A/B the risk of death was increased by 1.5 (95%-CI 1.1-2.1). Median OS in patients with IDH-mut gliomas without CDKN2A/B deletion was 92.0 months compared to 40.0 months with CDKN2A/B deletion (p < 0.001, Log-Rank). CDKN2A/B deletions were associated with a significantly shorter OS (HR = 3.2; 95%-CI 2.2-5.5). For p16 IHC analysis, 10 eligible studies with 1087 examined samples were included. The cut-off for retention differed between the studies. In 588/662 p16 retained cases CDKN2A/B deletions was not detected, implying a negative predictive value (NPV) of p16 staining of 88.8%. Conversely, 279/425 p16 absent cases showed a CDKN2A/B deletion resulting in a positive predictive value (PPV) of 65.6%. Sensitivity of p16 staining for CDKN2A/B detection was 79.0%, specificity 80.1%. Highest diagnostic accuracy of p16 IHC was reached with a cut-off of > 5% and within IDH-mut glioma.

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来源期刊
Acta Neuropathologica Communications
Acta Neuropathologica Communications Medicine-Pathology and Forensic Medicine
CiteScore
11.20
自引率
2.80%
发文量
162
审稿时长
8 weeks
期刊介绍: "Acta Neuropathologica Communications (ANC)" is a peer-reviewed journal that specializes in the rapid publication of research articles focused on the mechanisms underlying neurological diseases. The journal emphasizes the use of molecular, cellular, and morphological techniques applied to experimental or human tissues to investigate the pathogenesis of neurological disorders. ANC is committed to a fast-track publication process, aiming to publish accepted manuscripts within two months of submission. This expedited timeline is designed to ensure that the latest findings in neuroscience and pathology are disseminated quickly to the scientific community, fostering rapid advancements in the field of neurology and neuroscience. The journal's focus on cutting-edge research and its swift publication schedule make it a valuable resource for researchers, clinicians, and other professionals interested in the study and treatment of neurological conditions.
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