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通过微阵列分析鉴定神经鞘黏液瘤和神经鞘瘤的差异基因表达谱。

Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis.

机构信息

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1732, USA.

出版信息

Mod Pathol. 2011 Mar;24(3):343-54. doi: 10.1038/modpathol.2010.203. Epub 2011 Feb 4.

Abstract

Neurothekeomas and dermal nerve sheath myxomas have previously been considered related cutaneous neoplasms of peripheral nerve sheath origin based on light microscopic similarities. However, recent immunohistochemical and ultrastructural data indicate nerve sheath myxomas exhibit true nerve sheath differentiation, whereas no such compelling evidence exists for neurothekeomas. Although neurothekeomas lack a specific immunohistochemical profile, similar antigen expression and histopathologic patterns suggest neurothekeomas may be categorized as fibrohistiocytic tumors. To date, no known molecular studies have examined the histogenetic relationship of these tumors. We report the first microarray-based gene expression profile study of these entities on formalin-fixed paraffin-embedded tissues. Cases of dermal schwannomas, dermal nerve sheath myxomas, myxoid/mixed/cellular neurothekeomas, and cellular fibrous histiocytomas diagnosed in the past 3 years were identified in our database. Archival formalin-fixed paraffin-embedded tissue from 28 patients was selected for microarray analysis (seven schwannomas, five nerve sheath myxomas, nine myxoid/mixed/cellular neurothekeomas and seven cellular fibrous histiocytomas). Following tumor RNA isolation, amplification and labeling using commercially available kits, labeled targets were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array (Santa Clara, CA, USA). Acquisition of array images and data analyses was performed using appropriate software. Hierarchical clustering and principal component analysis demonstrated discrete groups, which correlated with histopathologically identified diagnoses. Dermal nerve sheath myxomas demonstrate very similar molecular genetic signatures to dermal schwannomas, whereas neurothekeomas of all subtypes more closely resemble cellular fibrous histiocytomas. We are the first to report distinct gene expression profiles for nerve sheath myxomas and neurothekeomas, which further substantiates the argument that these are separate entities. Our molecular data confirms that dermal nerve sheath myxomas are of peripheral nerve sheath origin, and suggests that neurothekeomas may actually be a variant of fibrous histiocytomas.

摘要

神经鞘黏液瘤和真皮神经鞘黏液瘤先前被认为是基于光镜相似性起源于外周神经鞘的相关皮肤肿瘤。然而,最近的免疫组织化学和超微结构数据表明神经鞘黏液瘤表现出真正的神经鞘分化,而神经鞘黏液瘤则没有这样令人信服的证据。尽管神经鞘黏液瘤缺乏特定的免疫组织化学特征,但相似的抗原表达和组织病理学模式表明神经鞘黏液瘤可能被归类为纤维组织细胞瘤。迄今为止,尚无已知的分子研究检查这些肿瘤的组织发生关系。我们报告了首例基于微阵列的这些实体的福尔马林固定石蜡包埋组织的基因表达谱研究。在我们的数据库中鉴定了过去 3 年中诊断的真皮施万细胞瘤、真皮神经鞘黏液瘤、黏液样/混合/细胞性神经鞘瘤和细胞纤维组织细胞瘤。从 28 名患者的存档福尔马林固定石蜡包埋组织中选择微阵列分析(7 例施万细胞瘤、5 例神经鞘黏液瘤、9 例黏液样/混合/细胞性神经鞘瘤和 7 例细胞纤维组织细胞瘤)。使用市售试剂盒进行肿瘤 RNA 分离、扩增和标记后,将标记的靶标杂交到 Affymetrix GeneChip Human Genome U133 Plus 2.0 Array(美国加利福尼亚州圣克拉拉)上。使用适当的软件进行阵列图像的获取和数据分析。层次聚类和主成分分析显示出离散的组,与组织病理学确定的诊断相关。真皮神经鞘黏液瘤与真皮施万细胞瘤具有非常相似的分子遗传特征,而所有亚型的神经鞘瘤更类似于细胞纤维组织细胞瘤。我们是第一个报道神经鞘黏液瘤和神经鞘瘤的独特基因表达谱的人,这进一步证实了这些是不同的实体。我们的分子数据证实了真皮神经鞘黏液瘤起源于周围神经鞘,并且表明神经鞘瘤实际上可能是纤维组织细胞瘤的一种变体。

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