[摘要]ATRX多克隆的鉴定及其在星形细胞瘤和胶质母细胞瘤中的应用

J. Diaz, Tatiana Scoggin, Jason A. Ramos
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引用次数: 0

摘要

简介:α地中海贫血/智力迟钝综合征x连锁(ATRX)在染色质调控和端粒维持中发挥作用。它调节组蛋白H3.3与端粒染色质的结合。ATRX也是DNA复制和修复、染色质高阶结构调控、基因转录调控等多种重要细胞通路的主要组成部分。在II/III级星形细胞瘤、少星形细胞瘤、少突胶质细胞瘤和胶质母细胞瘤中观察到ATRX缺失。在II/III级胶质瘤中,大多数ATRX‐缺失病例都有IDH1/2突变。通过免疫组化染色评估ATRX损失捕获了大多数突变,为神经病理学诊断提供了合理的敏感性。本研究以星形细胞瘤和胶质母细胞瘤组织为重点,分析了ATRX在多种组织中的特异性和敏感性。材料和方法:采用福尔马林固定石蜡包埋组织,采用标准脱蜡步骤进行免疫组化染色,并在高压锅(脱蜡室)中使用柠檬酸缓冲溶液进行热诱导回收。抗体孵育30分钟,HRP检测,DAB显影。采用半自动染色系统(intellpath)对载玻片进行染色。ATRX多克隆抗体[Biocare Medical, California, USA]用标准方案在载体中稀释至最佳浓度。结果:弥漫性和间变性星形细胞瘤的ATRX染色率为44%,胶质母细胞瘤的ATRX染色率为57%。此外,交叉反应性测试确定的ATRX多克隆在某些情况下可能会染色正常大脑。结论:ATRX多克隆在诊断脑肿瘤(特别是星形细胞瘤和胶质母细胞瘤)时显示出潜在的优势,即使可以观察到一些交叉反应。ATRX联合其他脑标记抗体可以提供更好的诊断脑肿瘤的工具。引文格式:Jose Jonathan Diaz, Tatiana Scoggin, Jason Ramos。ATRX多克隆的鉴定及免疫组织化学在星形细胞瘤和胶质母细胞瘤中的应用[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要第458期。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Abstract 458: Characterization of ATRX polyclonal, application of immunohistochemical analysis on astrocytoma and glioblastoma
Introduction: Alpha thalassemia/mental retardation syndrome X-linked (ATRX) plays a role in chromatin regulation and maintenance of telomeres. It regulates incorporation of histone H3.3 into telomeric chromatin. ATRX is also a major component of various essential cellular pathways such as DNA replication and repair, chromatin higher-order structure regulation, and gene transcriptional regulation. ATRX loss was observed in grades II/III astrocytomas, oligoastrocytomas, oligodendrogliomas, and glioblastomas. In grades II/III gliomas, most ATRX‐loss cases had IDH1/2 mutations. Assessment of ATRX loss by IHC staining captures the majority of mutations, giving a reasonable sensitivity in neuropathology diagnostics. In this study, the specificity and sensitivity of ATRX were analyzed on multiple tissues focusing on Astrocytoma and Glioblastoma tissues. Materials and Methods: IHC staining has been performed by using formalin-fixed paraffin-embedded tissue with standard deparaffinization steps and a heat-induced retrieval method using a citrate buffer solution in a pressure cooker (Decloaking chamber). Antibody was incubated for 30 minutes, followed by HRP detection and DAB solution for visualization. Slides were stained using semi-automated staining system (intelliPATH). ATRX polyclonal antibody [Biocare Medical, California, USA] diluted in a carrier at an optimal concentration with standard protocol. Results: ATRX stained 44% of diffuse and anaplastic astrocytoma and 57% of glioblastoma. Also, cross-reactivity testing determined ATRX polyclonal may stain normal brain in some cases. A more comprehensive data evaluation shown below: Conclusions: ATRX polyclonal shows a potential advantage when diagnosing brain tumors (especially astrocytoma and glioblastomas) even if some cross reactivity can be observed. ATRX in conjunction with other brain marker antibodies can offer a better tool in diagnosing brain tumors. Citation Format: Jose Jonathan Diaz, Tatiana Scoggin, Jason Ramos. Characterization of ATRX polyclonal, application of immunohistochemical analysis on astrocytoma and glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 458.
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