Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas.
Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas.
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ATRX和IDH1-R132H免疫组化检测211对胶质瘤进展情况
DOI：
10.18632/oncotarget.7650
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发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Jiang T
中科院分区：
文献类型：
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作者：
Cai J;Zhu P;Zhang C;Li Q;Wang Z;Li G;Wang G;Yang P;Li J;Han B;Jiang C;Sun Y;Jiang T
胶质瘤的复发和向高级别发展是胶质瘤演变过程中的重要生物学事件和特征性行为。一小部分残留的细胞总是逃脱手术和放化疗，导致典型的致命性肿瘤复发或进展。IDH突变（异柠檬酸脱氢酶）和ATRX（α-地中海贫血/精神发育迟滞，X连锁）缺失/突变相关发生，可能代表神经胶质瘤发展中的早期遗传改变。然而，它们在胶质瘤演变中的预后价值仍需进一步研究。我们的研究包括211例胶质瘤的连续样本。我们采用免疫组织化学（IHC）方法检测了胶质瘤中IDH 1-R132 H突变和ATRX状态，结果表明IDH 1-R132 H和（或）ATRX状态可能是胶质瘤“综合诊断”所必需的基础分子信息。我们通过IDH 1-R132 H结合ATRX免疫组化阐明了胶质瘤进展的评估公式，并确定了IDH 1-R132 H/ATRX丢失与胶质瘤患者较长的进展时间间隔的相关性。此外，我们观察到大多数复发性肿瘤与其匹配的原发性肿瘤具有一致的IDH 1和ATRX状态，并证明了II级星形细胞瘤/少突胶质细胞瘤和伴有或不伴有IDH 1-R132 H的间变性少突星形细胞瘤的进展模式。在原发性-复发性胶质瘤中鉴定IDH 1-R132 H和ATRX缺失状态可能有助于治疗策略选择、治疗试验设计和临床预后评估。
Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. A small residual population of cells always escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence or progression. IDH mutation (isocitrate dehydrogenase) and ATRX (alpha-thalassemia/mental retardation, X-linked) loss/mutation occur in association and may represent early genetic alterations in the development of gliomas. However, their prognostic value in the evolution of gliomas still needs further investigation. Two hundreds and eleven serial sampling of gliomas were included in our study. We used immunohistochemistry (IHC) to detect IDH1-R132H mutation and ATRX status and showed that the IDH1-R132H and (or) ATRX status could be necessary to provide the basic molecular information for the “integrated diagnosis” of gliomas. We illustrated an evaluation formula for the evolution of gliomas by IDH1-R132H combined with ATRX immunohistochemistry and identified the association of IDH1-R132H/ATRX loss accompanied by longer progression time interval of patients with gliomas. Furthermore, we observed that most recurrences had a consistent IDH1 and ATRX status with their matched primary tumors and demonstrated the progressive pattern of grade II astrocytoma/oligodendroglial tumors and anaplastic oligoastrocytoma with or without IDH1-R132H. Identification of IDH1-R132H and ATRX loss status in the primary-recurrent gliomas may aid in treatment strategy selection, therapeutic trial design, and clinical prognosis evaluation.