Histological profile of tumours from MYCN transgenic mice

Histological profile of tumours from MYCN transgenic mice
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DOI:
10.1136/jcp.2007.054627
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发表时间:
2008-10-01
影响因子:
3.4
通讯作者:
Tweddle, D. A.
Tweddle, D. A.
中科院分区:
医学3区
文献类型:
--
作者:
Moore, H. C.;Wood, K. M.;Tweddle, D. A.

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背景:MYCN是人类神经母细胞瘤中最常见的扩增基因。目的:研究MYCN转基因小鼠神经母细胞瘤的组织病理学特征。方法:对27例来自半合子转基因小鼠的神经母细胞瘤和4例来自纯合子小鼠的神经母细胞瘤进行组织学检查;对24例肿瘤进行Ki 67和MYCN免疫细胞化学染色。从MYCN转基因小鼠中获得的肿瘤类似于人类神经母细胞瘤,显示出许多与间质贫乏神经母细胞瘤相关的特征,包括分化的异质性(但未观察到明显的神经节分化),低水平的许旺氏间质和高有丝分裂核破裂指数。肿瘤的Ki 67标记指数中位数为70%;所有肿瘤均表达MYCN,标记指数中位数为68%。鼠和人神经母细胞瘤之间最显著的差异是转基因小鼠肿瘤中存在易染体巨噬细胞,反映了高水平的细胞凋亡。这还没有以前被描述在人类或其他小鼠神经母细胞瘤models.Conclusions:这些研究突出了肿瘤从MYCN转基因小鼠和人类神经母细胞瘤之间的组织学相似性,并重申其作为一个有价值的模型来研究侵袭性人类神经母细胞瘤的生物学的作用。
Background: MYCN is the most commonly amplified gene in human neuroblastomas. This proto-oncogene has been overexpressed in a mouse model of the disease in order to explore the role of MYCN in this tumour.Aims: To report the histopathological features of neuroblastomas from MYCN transgenic mice.Methods: 27 neuroblastomas from hemizygous transgenic mice and four tumours from homozygous mice were examined histologically; Ki67 and MYCN immunocytochemistry was performed in 24 tumours.Results: Tumours obtained from MYCN transgenic mice resembled human neuroblastomas, displaying many of the features associated with stroma-poor neuroblastoma, including heterogeneity of differentiation (but no overt ganglionic differentiation was seen), low levels of Schwannian stroma and a high mitosis karyorrhexis index. The tumours had a median Ki67 labelling index of 70%; all tumours expressed MYCN with a median labelling index of 68%. The most striking difference between the murine and human neuroblastomas was the presence of tingible body macrophages in the transgenic mouse tumours reflecting high levels of apoptosis. This has not previously been described in human or other murine neuroblastoma models.Conclusions: These studies highlight the histological similarities between tumours from MYCN transgenic mice and human neuroblastomas, and reaffirm their role as a valuable model to study the biology of aggressive human neuroblastoma.