Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology
Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology
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DOI：
10.1002/cncy.21269
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发表时间：
2013-08-01
影响因子：
3.4
通讯作者：
Tsujimura, Tohru
中科院分区：
文献类型：
--
作者：
Matsumoto, Shinji;Nabeshima, Kazuki;Tsujimura, Tohru
恶性胸膜间皮瘤（MPM），大多数患者首先表现为胸腔积液，因此，细胞学分析是主要的诊断方法。然而，细胞学MPM和反应性间皮细胞（RMCs）之间的区别，在积液可能是非常困难的，由于缺乏完善的免疫细胞化学标记物和明确的细胞学标准MPM。此外，来自同一患者的渗出液中MPM细胞和RMC两者的存在使得分化更具挑战性。9 p21位点的纯合性缺失，该位点的细胞周期蛋白依赖性激酶抑制剂2A/p16（CDKN 2A/p16）基因，经常发生在MPM，但从来没有报道在RMCs。本研究的目的是确定MPM细胞的细胞形态学特征，通过荧光原位杂交（FISH）鉴定的9 p21纯合性缺失的存在。方法为此目的，使用虚拟显微镜系统记录涂片制备的细胞，并进行FISH分析。此后，9 p21纯合缺失阳性细胞被确定在记录的虚拟slides，其次是他们的形态学features.Results分析间皮瘤细胞的9 p21纯合缺失阳性表现出显着更频繁的细胞中细胞吞噬，多核（2个以上的核），和更大的多细胞簇组成的10个以上的细胞比9 p21缺失阴性RMCs。可能的截断值也提出了这些形态学标记，以区分MPM细胞从RMCs.CONCLUSIONS这些形态学差异和截断值是有用的间皮瘤细胞从RMCs的细胞学分化。此外，虚拟显微镜和荧光原位杂交相结合的新技术被引入肿瘤形态学分析。癌症（癌症细胞病理学）2013;121：415-22。(c)9 p21缺失阳性恶性胸膜间皮瘤细胞的形态学分析揭示了可用于从反应性间皮瘤细胞分化的细胞学特征。此外，虚拟显微镜和荧光原位杂交相结合的新技术被引入肿瘤形态学分析。
BACKGROUND In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH).METHODS For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion-positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics.RESULTS Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cell-in-cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion-negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs.CONCLUSIONS These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis. Cancer (Cancer Cytopathol) 2013;121:415-22. (c) 2013 American Cancer Society.Morphological analysis of 9p21 deletion-positive malignant pleural mesothelioma cells reveals cytological characteristics useful for differentiation from reactive mesothelial cells. In addition, the novel technique of a combination of virtual microscopy and fluorescent in situ hybridization is introduced for tumor morphological analysis.