de Wit Sanne, Manicone Mariangela, Rossi Elisabetta, Lampignano Rita, Yang Liwen, Zill Beate, Rengel-Puertas Alvera, Ouhlen Marianne, Crespo Mateus, Berghuis Anne Margreet Sofie, Andree Kiki Carlijn, Vidotto Riccardo, Trapp Elisabeth Katharina, Tzschaschel Marie, Colomba Emeline, Fowler Gemma, Flohr Penelope, Rescigno Pasquale, Fontes Mariane Sousa, Zamarchi Rita, Fehm Tanja, Neubauer Hans, Rack Brigitte, Alunni-Fabbroni Marianna, Farace Françoise, De Bono Johann, IJzerman Maarten Joost, Terstappen Leonardus Wendelinus Mathias Marie
Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, MIRA Institute, University of Twente, Enschede, The Netherlands.
Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Oncotarget. 2018 Nov 2;9(86):35705-35716. doi: 10.18632/oncotarget.26298.
The presence of high expressing epithelial cell adhesion molecule (EpCAM) circulating tumor cells (CTC) enumerated by CellSearch in blood of cancer patients is strongly associated with poor prognosis. This raises the question about the presence and relation with clinical outcome of low EpCAM expressing CTC (EpCAM CTC). In the EU-FP7 CTC-Trap program, we investigated the presence of EpCAM and EpCAM CTC using CellSearch, followed by microfiltration of the EpCAM CTC depleted blood. Blood samples of 108 castration-resistant prostate cancer patients and 22 metastatic breast cancer patients were processed at six participating sites, using protocols and tools developed in the CTC-Trap program. Of the prostate cancer patients, 53% had ≥5 EpCAM CTC and 28% had ≥5 EpCAM CTC. For breast cancer patients, 32% had ≥5 EpCAM CTC and 36% had ≥5 EpCAM CTC. 70% of prostate cancer patients and 64% of breast cancer patients had in total ≥5 EpCAM and/or EpCAM CTC, increasing the number of patients in whom CTC are detected. Castration-resistant prostate cancer patients with ≥5 EpCAM CTC had shorter overall survival versus those with <5 EpCAM CTC ( = 0.000). However, presence of EpCAM CTC had no relation with overall survival. This emphasizes the importance to demonstrate the relation with clinical outcome when presence of CTC identified with different technologies are reported, as different CTC subpopulations can have different relations with clinical outcome.
通过CellSearch检测出癌症患者血液中高表达上皮细胞粘附分子(EpCAM)的循环肿瘤细胞(CTC)与预后不良密切相关。这就引出了关于低表达EpCAM的CTC(EpCAM CTC)的存在及其与临床结局关系的问题。在欧盟第七框架计划的CTC-Trap项目中,我们使用CellSearch检测EpCAM和EpCAM CTC的存在情况,随后对去除EpCAM CTC的血液进行微滤。108例去势抵抗性前列腺癌患者和22例转移性乳腺癌患者的血样在六个参与站点进行处理,使用的是CTC-Trap项目开发的方案和工具。在前列腺癌患者中,53%有≥5个EpCAM CTC,28%有≥5个EpCAM CTC。对于乳腺癌患者,32%有≥5个EpCAM CTC,36%有≥5个EpCAM CTC。70%的前列腺癌患者和64%的乳腺癌患者总共至少有5个EpCAM和/或EpCAM CTC,这增加了检测到CTC的患者数量。≥5个EpCAM CTC的去势抵抗性前列腺癌患者的总生存期短于<5个EpCAM CTC的患者( = 0.000)。然而,EpCAM CTC的存在与总生存期无关。这强调了在报告用不同技术鉴定出的CTC存在情况时,证明其与临床结局关系的重要性,因为不同的CTC亚群与临床结局可能有不同的关系。