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Thyroid transcription factor-1 distinguishes subependymal giant cell astrocytoma from its mimics and supports its cell origin from the progenitor cells in the medial ganglionic eminence.

甲状腺转录因子-1(TTF-1)能鉴别室管膜下巨细胞性星形细胞瘤(SEGA)与其类似肿瘤,并支持其细胞来源于内侧神经节隆起中的祖细胞。

Hang JF,Hsu CY,Lin SC,Wu CC,Lee HJ,Ho DM
阅读:559 Modern PathologyMar 2017; 30 (3): 316 - 469:318-328 

Abstract

Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker. We then examined TTF-1 expression in non-neoplastic brain tissue to determine the cell origin of subependymal giant cell astrocytoma. Twenty-four subependymal giant cell astrocytoma specimens were subjected to tissue microarray construction. For comparison, a selection of tumors, including histologic mimics (21 gemistocytic astrocytomas and 24 gangliogliomas), tumors predominantly occurring at the ventricular system (50 ependymomas, 19 neurocytomas, and 7 subependymomas), and 134 astrocytomas (3 pleomorphic xanthoastrocytomas, 45 diffuse astrocytomas, 46 anaplastic astrocytomas, and 40 glioblastomas) were used. Immunohistochemical stain for TTF-1 was positive in all 24 subependymal giant cell astrocytomas, whereas negative in all astrocytomas, gangliogliomas, ependymomas, and subependymomas. Neurocytomas were positive for TTF-1 in 4/19 (21%) of cases using clone 8G7G3/1 and in 9/19 (47%) of cases using clone SPT24. In the three fetal brains that we examined, TTF-1 expression was seen in the medial ganglionic eminence, a transient fetal structure between the caudate nucleus and the thalami. There was no BRAF(V600E) mutation identified by direct sequencing in the 20 subependymal giant cell astrocytomas that we studied. In conclusion, TTF-1 is a useful marker in distinguishing subependymal giant cell astrocytoma from its mimics. Expression of TTF-1 in the fetal medial ganglionic eminence indicates that subependymal giant cell astrocytoma may originate from the progenitor cells in this region.

摘要

室管膜下巨细胞性星形细胞瘤(SEGA)是大脑内的良性肿瘤,且主要与结节性硬化症相关。不过,由于SEGA中存在明显的多形性大肿瘤细胞并偶伴有非典型性特征,如肿瘤坏死,内皮增生,可能会被误认为是其它高级别的恶性大脑肿瘤。

本研究中,为确定TTF-1的诊断功能,我们首先研究了TTF-1在大系列的SEGA及发生于相同部位、组织学相似肿瘤中的表达。随后我们研究了TTF-1在非肿瘤大脑组织中的表达,以确定SEGA肿瘤细胞的来源。24例SEGA标本用于构建组织芯片。对照组为与SEGA组织学及发生部位类似的肿瘤,包括组织学类似肿瘤(21例原浆性星形细胞瘤及24例神经节细胞胶质瘤),主要发生于脑室系统的肿瘤(50例室管膜瘤,19例中枢神经细胞瘤以及7例室管膜下瘤),以及134例星形细胞瘤(3例多形性黄色星形细胞瘤,45例弥漫性星形胶质细胞瘤,46例间变性星形胶质细胞瘤,以及40例胶质母细胞瘤。

TTF-1的免疫组化表明,24例SEGA中TTF-1均为阳性,而所有的星形细胞瘤、神经节细胞胶质瘤、室管膜瘤及室管膜下瘤均为阴性。约21%的中枢神经细胞瘤(4/19)克隆号:8G7G3/1的TTF-1阳性,而47%(9/19)的中枢神经细胞瘤克隆号 SPT24的TTF-1阳性。

在我们检测的三例胎脑组织中,TTF-1表达于内侧神经节隆起--一种位于尾状核和丘脑之间的过渡性胎儿脑结构。在我们研究的20例SEGA病例中,通过直接测序并未能发现BRAF(V600E)突变。

总之,TTF-1是鉴别SEGA及其类似肿瘤的有用标志,TTF-1在胚胎内侧神经节隆起中表达表明SEGA可能源于此区域中的祖细胞。

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