转移性乳腺癌中肿瘤衍生细胞外囊泡和循环肿瘤细胞的 HER2 表达。
HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer.
机构信息
Department of Medical Cell BioPhysics, Faculty of Science and Technology, University of Twente, Carré Room CR4433, Hallenweg 23, 7522 NH, Enschede, The Netherlands.
Department of Medical Oncology, Institut Curie, PSL Research University, Paris and Saint Cloud, France.
出版信息
Breast Cancer Res. 2020 Aug 12;22(1):86. doi: 10.1186/s13058-020-01323-5.
BACKGROUND
Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients.
METHODS
Blood samples from 98 patients (CLCC-IC-2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch images using the open-source ACCEPT software.
RESULTS
CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2-, CK-HER2+, and CK+HER2+. The inclusion of anti-HER2 increased the percentage of informative samples with ≥ 1 detectable CTC from 89 to 95%. CK- CTCs and tdEVs correlated equally well with the clinical outcome as CK+ CTCs and tdEVs. Inter- and intra-patient heterogeneity was found for the CTC/tdEV phenotypes, and the presence of 2 or 3 classes of CTCs/tdEVs was associated with worse prognosis compared to a uniform CTC/tdEV phenotype present (1 class). The use of ≥ 7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity using the HER2 amplification status of the primary tumor as a classification variable.
CONCLUSIONS
HER2 can be detected on CTCs and tdEVs not expressing CK, and these CK- CTCs/tdEVs have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the primary tissue. CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival.
背景
转移性癌症患者血液中的肿瘤衍生细胞外囊泡（tdEVs）和循环肿瘤细胞（CTCs）与不良预后相关。在这项研究中，我们探索了转移性乳腺癌患者的 CTCs 和 tdEVs 上的人类表皮生长因子受体 2（HER2）表达。
方法
98 名患者的血液样本（CLCC-IC-2006-04 研究）最初使用 CellSearch®系统处理，使用 CTC 试剂盒和抗 HER2 作为染色鸡尾酒中的额外标记物。使用开源 ACCEPT 软件从生成的 CellSearch 图像中自动计数 CTCs 和 tdEVs。
结果
根据细胞角蛋白（CK）和 HER2 表型将 CTCs 和 tdEVs 分为 CK+HER2-、CK-HER2+和 CK+HER2+。包含抗 HER2 可将可检测到的≥1个 CTC 的信息样本百分比从 89%提高到 95%。CK-CTCs 和 tdEVs 与 CK+CTCs 和 tdEVs 一样与临床结果相关。CTCs/tdEV 表型存在患者间和患者内异质性，与存在单一 CTC/tdEV 表型（1 类）相比，存在 2 或 3 类 CTCs/tdEVs 与预后较差相关。使用≥7%的 HER2+CK+tdEV 可以预测组织中 HER2 的表达，使用原发性肿瘤的 HER2 扩增状态作为分类变量，其敏感性和特异性分别为 74%。
结论
HER2 可以在不表达 CK 的 CTCs 和 tdEVs 上检测到，这些 CK-CTCs/tdEVs 与表达 CK 的 CTCs 和 tdEVs 具有相似的临床相关性。tdEVs 在预测原发性组织的 HER2 状态方面优于 CTCs。患者血液中的 CTC 和 tdEV 异质性与总生存期呈反比相关。
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