Lampignano Rita, Schneck Helen, Neumann Martin, Fehm Tanja, Neubauer Hans
Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Duesseldorf, Germany.
Forschungslabore der Frauenklinik des, Universitätsklinikums Düsseldorf, Life Science Center, Merowingerplatz 1A, 40225, Düsseldorf, Germany.
Adv Exp Med Biol. 2017;994:181-203. doi: 10.1007/978-3-319-55947-6_10.
The presence of EpCAM-positive circulating tumor cells (CTCs) in the peripheral blood is associated with poor clinical outcomes in breast, colorectal and prostate cancer, as well as the prognosis of other tumor types. In addition, recent studies have suggested that the presence of CTCs undergoing epithelial-to-mesenchymal transition and, as such, may exhibit reduced or no expression of epithelial proteins e.g. EpCAM, might be related to disease progression in metastatic breast cancer (MBC) patients. Analyzing the neoplastic nature of this EpCAM-low/negative (EpCAM-neg) subpopulation remains an open issue as the current standard detection methods for CTCs are not efficient at identifying this subpopulation of cells. The possible association of EpCAM-neg CTCs with EpCAM-positive (EpCAM-pos) CTCs and role in the clinicopathological features and prognosis of MBC patients has still to be demonstrated. Several technologies have been developed and are currently being tested for the identification and the downstream analyses of EpCAM-pos CTCs. These technologies can be adapted and implemented into workflows to isolate and investigate EpCAM-neg cells to understand their biology and clinical relevance. This chapter will endeavour to explain the rationale behind the identification and analyses of all CTC subgroups, as well as to review the current strategies employed to enrich, isolate and characterize EpCAM-negative CTCs. Finally, the latest findings in the field will briefly be discussed with regard to their clinical relevance.
外周血中上皮细胞黏附分子（EpCAM）阳性循环肿瘤细胞（CTC）的存在与乳腺癌、结直肠癌和前列腺癌的不良临床结局以及其他肿瘤类型的预后相关。此外，最近的研究表明，经历上皮-间质转化的CTC的存在，因此可能表现出上皮蛋白（如EpCAM）表达降低或无表达，这可能与转移性乳腺癌（MBC）患者的疾病进展有关。由于目前CTC的标准检测方法在识别这种细胞亚群方面效率不高，分析这种EpCAM低表达/阴性（EpCAM-neg）亚群的肿瘤性质仍然是一个悬而未决的问题。EpCAM阴性CTC与EpCAM阳性（EpCAM-pos）CTC的可能关联及其在MBC患者临床病理特征和预后中的作用仍有待证实。已经开发了几种技术，目前正在测试用于EpCAM阳性CTC的识别和下游分析。这些技术可以进行调整并应用于工作流程，以分离和研究EpCAM阴性细胞，了解它们的生物学特性和临床相关性。本章将努力解释所有CTC亚群识别和分析背后的基本原理，并回顾目前用于富集、分离和表征EpCAM阴性CTC的策略。最后，将简要讨论该领域的最新发现及其临床相关性。
