Xu Lu, Jia Songlin, Li Hengyu, Yu Yue, Liu Guoping, Wu Yanmei, Liu Xishui, Liu Chaoqian, Zhou Yue, Zhang Zhenzhen, Sheng Yuan
Department of Breast Surgery, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China.
Biotecan Medical Diagnostics Co., Ltd., Zhangjiang Center for Translational Medicine, Shanghai 201204, P.R. China.
Oncol Lett. 2018 Feb;15(2):2522-2528. doi: 10.3892/ol.2017.7540. Epub 2017 Dec 6.
Identification of circulating tumor cells (CTCs) by surface marker expression and ploidy analysis [immunostaining-fluorescence hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90.76%) by the iFISH system. Higher CTC counts and sensitivity were observed in patients with increased tumor size burden and unfavorable hormone receptor status. Investigation of CTC subtypes based on ploidy analysis indicated that triploid CTCs constituted the majority of CTCs evaluated. While CK-positive CTCs were detected in a small cohort of patients, an overall low rate of CK expression was observed in the 18 patient samples evaluated. Of note, CK expression was rare in CTCs detected in patients with Herceptin 2 (Her2)-positive or triple-negative [estrogen receptor (ER)-, progesterone receptor (PR)- and Her2-negative], indicating that lack of ER and PR may result in promotion of epithelial-mesenchymal transition and enhancement of tumor aggression.
通过表面标志物表达和倍性分析[免疫染色-荧光杂交（iFISH）]来鉴定循环肿瘤细胞（CTC），已被证明是一种在鉴定某些实体癌方面高度敏感的方法。在本研究中，进行了iFISH分析以鉴定184例新诊断的非转移性乳腺癌患者中的CTC，并根据细胞角蛋白（CK）表达和倍性状态对CTC亚型的分布进行了表征。结果显示，对于非转移性、非整倍体乳腺癌的CTC，无论CK表达谱如何，iFISH系统均可高灵敏度（90.76%）地检测到。在肿瘤大小负担增加和激素受体状态不佳的患者中观察到更高的CTC计数和灵敏度。基于倍性分析对CTC亚型的研究表明，三倍体CTC占评估的CTC的大多数。虽然在一小部分患者中检测到了CK阳性的CTC，但在评估的18例患者样本中观察到总体CK表达率较低。值得注意的是，在人表皮生长因子受体2（Her2）阳性或三阴性[雌激素受体（ER）、孕激素受体（PR）和Her2阴性]患者中检测到的CTC中，CK表达很少，这表明ER和PR的缺乏可能导致上皮-间质转化的促进和肿瘤侵袭性增强。
