Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children’s Cancer Group

Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children’s Cancer Group
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在 GLI3 阳性髓母细胞瘤中,拓扑异构酶 IIβ 免疫反应性 (IR) 与神经元标记物 -IR 共定位,但与胶质纤维酸性蛋白 -IR 不共定位:对日本儿童癌症组 124 例髓母细胞瘤的免疫组织化学分析

DOI:
10.1007/s10014-021-00396-0
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发表时间:
2021
影响因子:
3.3
通讯作者:
Watanabe Hiroyoshi
Watanabe Hiroyoshi
中科院分区:
医学3区
文献类型:
--
作者:
Miyahara Hiroaki;Natsumeda Manabu;Kanemura Yonehiro;Yamasaki Kai;Riku Yuichi;Akagi Akio;Oohashi Wataru;Shofuda Tomoko;Yoshioka Ema;Sato Yuya;Taga Takashi;Naruke Yuki;Ando Ryo;Hasegawa Daiichiro;Yoshida Makiko;Sakaida Tsukasa;Okada Naoki;Watanabe Hiroyoshi

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我们以前曾报道过在表达神经元标记物(NM)和/或胶质细胞酸性蛋白(GFAP)的髓母细胞瘤中观察到GLI 3。此外,表达NM或GFAP的髓母细胞瘤患者分别倾向于显示良好或不良预后。在本研究中,我们重点关注拓扑异构酶IIβ(TOP 2 β)作为髓母细胞瘤神经元分化的可能调节因子的作用,并在更大的人群中检测GLI 3、NM、GFAP和TOP 2 β表达的病理作用。我们根据对NM和GFAP的免疫反应性(IR)将124例髓母细胞瘤分为三组(NM-/GFAP-、NM +/GFAP-和GFAP +)。使用荧光免疫染色和公开可用的单细胞RNA测序数据集评估GLI 3、NM、GFAP和TOP 2 β之间的关系。总共有87例、30例和7例髓母细胞瘤被分类为NM-/GFAP-、NM + /GFAP-和GFAP +,分别显示中等、良好和差的增生。GLI 3-IR常见于NM +/GFAP−和GFAP +,TOP 2 β-IR常见于NM +/GFAP−髓母细胞瘤。在荧光免疫染色中,TOP2β-IR主要与NeuN-IR共定位,而与GFAP-IR不共定位;在单细胞RNA测序中,TOP2β在CMAS/DCX阳性的细胞中表达增高,而在GFAP阳性的细胞中不表达。NM-IR和GFAP-IR对判断髓母细胞瘤患者的预后有重要意义,应在临床实践中进行评估。
We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM−/GFAP−, NM +/GFAP−, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM−/GFAP−, NM + /GFAP−, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP−  and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP−  medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing,TOP2βexpression was elevated inCMAS/DCX-positive, but not inGFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.
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