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黑色素瘤细胞中的核假包涵体:预后因素还是假象?高尔基体磷蛋白3过表达在核假包涵体形成中的可能作用。

Nuclear pseudoinclusions in melanoma cells: prognostic fact or artifact? The possible role of Golgi phosphoprotein 3 overexpression in nuclear pseudoinclusions generation.

作者信息

Donizy Piotr, Kaczorowski Maciej, Biecek Przemyslaw, Halon Agnieszka, Matkowski Rafal

机构信息

Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.

Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland.

出版信息

Pathol Int. 2018 Feb;68(2):117-122. doi: 10.1111/pin.12629. Epub 2018 Jan 29.

Abstract

Nuclear pseudoinclusions (NPIs) are classically found in papillary thyroid carcinoma and meningioma. Although NPIs have been described in melanocytic lesions, there is no systematic analysis of potential relationship between NPIs and other clinicopathological characteristics of melanoma. We examined the presence of NPIs in H&E-stained tissue sections form 96 melanomas and analyzed statistical associations with important clinicopathological parameters and tissue immunoreactivity for selected proteins involved in epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and mobility (ALCAM, ADAM-10), regulation of mitosis (PLK1), cell survival (FOXP1) and functioning of Golgi apparatus (GOLPH3, GP73). NPIs were observed in 20% of melanomas and their presence correlated with high mitotic rate and ulceration of the tumor, but not with Breslow thickness, histologic type, or presence of metastases. We observed a significant correlation with shorter cancer-specific survival, but not disease-free survival. Presence of NPIs was related to high expression of GOLPH3 in melanoma cells, whereas their absence was linked to enhanced immunoreactivity of GOLPH3 in tumor-associated macrophages. NPIs are not an uncommon finding in skin melanoma and their diagnostic and prognostic utility could be helpful in the daily routine histopathological practice. The possible explanation of NPI generation is associated with enhanced activity of Golgi apparatus in melanoma cells.

摘要

核假包涵体(NPIs)经典地见于甲状腺乳头状癌和脑膜瘤。尽管NPIs已在黑素细胞性病变中被描述,但尚无对NPIs与黑色素瘤其他临床病理特征之间潜在关系的系统分析。我们检查了96例黑色素瘤的苏木精-伊红(H&E)染色组织切片中NPIs的存在情况,并分析了其与重要临床病理参数以及参与上皮-间质转化(SPARC、N-钙黏蛋白)、细胞黏附和迁移(活化白细胞黏附分子、解聚素和金属蛋白酶10)、有丝分裂调控(极光激酶1)、细胞存活(叉头框蛋白P1)和高尔基体功能(高尔基体磷蛋白3、高尔基体磷酸化蛋白73)的选定蛋白质的组织免疫反应性之间的统计学关联。在20%的黑色素瘤中观察到NPIs,其存在与肿瘤的高有丝分裂率和溃疡相关,但与Breslow厚度、组织学类型或转移的存在无关。我们观察到其与较短的癌症特异性生存期有显著相关性,但与无病生存期无关。NPIs的存在与黑色素瘤细胞中高尔基体磷蛋白3的高表达相关,而其不存在则与肿瘤相关巨噬细胞中高尔基体磷蛋白3的免疫反应性增强有关。NPIs在皮肤黑色素瘤中并非罕见发现,其诊断和预后价值可能有助于日常常规组织病理学实践。NPIs产生的可能解释与黑色素瘤细胞中高尔基体活性增强有关。

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