Cohen Evan N, Jayachandran Gitanjali, Moore Richard G, Cristofanilli Massimo, Lang Julie E, Khoury Joseph D, Press Michael F, Kim Kyu Kwang, Khazan Negar, Zhang Qiang, Zhang Youbin, Kaur Pushpinder, Guzman Roberta, Miller Michael C, Reuben James M, Ueno Naoto T
Department of Hematopathology Research, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
Cancers (Basel). 2022 Oct 26;14(21):5238. doi: 10.3390/cancers14215238.
Circulating tumor cells (CTCs) captured from the blood of cancer patients may serve as a surrogate source of tumor material that can be obtained via a venipuncture (also known as a liquid biopsy) and used to better understand tumor characteristics. However, the only FDA-cleared CTC assay has been limited to the enumeration of surface marker-defined cells and not further characterization of the CTCs. In this study, we tested the ability of a semi-automated device capable of capturing and harvesting CTCs from peripheral blood based on cell size and deformability, agnostic of cell-surface markers (the Parsortix PC1 System), to yield CTCs for evaluation by downstream techniques commonly available in clinical laboratories. The data generated from this study were used to support a De Novo request (DEN200062) for the classification of this device, which the FDA recently granted. As part of a multicenter clinical trial, peripheral blood samples from 216 patients with metastatic breast cancer (MBC) and 205 healthy volunteers were subjected to CTC enrichment. A board-certified pathologist enumerated the CTCs from each participant by cytologic evaluation of Wright-Giemsa-stained slides. As proof of principle, cells harvested from a concurrent parallel sample provided by each participant were evaluated using one of three additional evaluation techniques: molecular profiling by qRT-PCR, RNA sequencing, or cytogenetic analysis of HER2 amplification by FISH. The study demonstrated that the Parsortix PC1 System can effectively capture and harvest CTCs from the peripheral blood of MBC patients and that the harvested cells can be evaluated using orthogonal methodologies such as gene expression and/or Fluorescence In Situ Hybridization (FISH).
从癌症患者血液中捕获的循环肿瘤细胞（CTC）可作为肿瘤物质的替代来源，通过静脉穿刺（也称为液体活检）获取，用于更好地了解肿瘤特征。然而，唯一获得美国食品药品监督管理局（FDA）批准的CTC检测方法仅限于对表面标志物定义的细胞进行计数，而无法对CTC进行进一步表征。在本研究中，我们测试了一种半自动设备（Parsortix PC1系统）的能力，该设备能够基于细胞大小和可变形性从外周血中捕获和收获CTC，而不依赖于细胞表面标志物，从而获得CTC以供临床实验室常用的下游技术进行评估。本研究产生的数据用于支持该设备分类的全新申请（DEN200062），FDA最近批准了该申请。作为一项多中心临床试验的一部分，对216例转移性乳腺癌（MBC）患者和205名健康志愿者的外周血样本进行了CTC富集。一名获得董事会认证的病理学家通过对瑞氏-吉姆萨染色玻片的细胞学评估，对每个参与者的CTC进行计数。作为原理验证，使用三种额外评估技术之一对每个参与者同时提供的平行样本中收获的细胞进行评估：通过qRT-PCR进行分子谱分析、RNA测序或通过FISH对HER2扩增进行细胞遗传学分析。该研究表明，Parsortix PC1系统可以有效地从MBC患者的外周血中捕获和收获CTC，并且收获的细胞可以使用基因表达和/或荧光原位杂交（FISH）等正交方法进行评估。
