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MYCN转基因小鼠肿瘤的组织学特征

Histological profile of tumours from MYCN transgenic mice.

作者信息

Moore H C, Wood K M, Jackson M S, Lastowska M A, Hall D, Imrie H, Redfern C P F, Lovat P E, Ponthan F, O'Toole K, Lunec J, Tweddle D A

机构信息

Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

出版信息

J Clin Pathol. 2008 Oct;61(10):1098-103. doi: 10.1136/jcp.2007.054627. Epub 2008 Aug 4.

Abstract

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.

摘要

背景

MYCN是人类神经母细胞瘤中最常扩增的基因。为了探究MYCN在该肿瘤中的作用,这个原癌基因已在该疾病的小鼠模型中过度表达。

目的

报告MYCN转基因小鼠神经母细胞瘤的组织病理学特征。

方法

对来自半合子转基因小鼠的27个神经母细胞瘤和来自纯合子小鼠的4个肿瘤进行组织学检查;对24个肿瘤进行Ki67和MYCN免疫细胞化学检测。

结果

从MYCN转基因小鼠获得的肿瘤类似于人类神经母细胞瘤,表现出许多与低基质神经母细胞瘤相关的特征,包括分化异质性(但未见明显的神经节分化)、施万细胞基质水平低和高有丝分裂核溶解指数。这些肿瘤的Ki67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%。小鼠和人类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吞噬细胞,这反映了高水平的细胞凋亡。此前在人类或其他小鼠神经母细胞瘤模型中尚未有过此类描述。

结论

这些研究突出了MYCN转基因小鼠肿瘤与人类神经母细胞瘤之间的组织学相似性,并重申了它们作为研究侵袭性人类神经母细胞瘤生物学的有价值模型的作用。

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