Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK.
Br J Cancer. 2012 Jan 31;106(3):508-16. doi: 10.1038/bjc.2011.545. Epub 2011 Dec 20.
Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study.
Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms.
ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0-240) vs 0 (range 0-144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms.
ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.
获取用于胰腺癌诊断和生物标志物评估以辅助药物开发的组织具有挑战性。循环肿瘤细胞(CTC)可能代表一种潜在的生物标志物,可以满足这些未满足的需求。我们在一项初步探索性研究中前瞻性比较了两种用于胰腺癌患者 CTC 计数和特征分析的平台的效用。
前瞻性采集了 54 名同意患者的血液样本,并通过 CellSearch 和大小分离上皮肿瘤细胞(ISET)进行分析。CellSearch 利用免疫磁捕获表达上皮标志物的 CTC,而 ISET 是一种独立于标志物的血液过滤装置。评估循环肿瘤细胞上皮和间充质标志物的表达,以探索两种平台之间 CTC 数量的任何差异。
ISET 比 CellSearch 检测到更多的患者(93%比 40%)和更多的 CTC(中位数 CTCs/7.5ml,9(范围 0-240)比 0(范围 0-144))。在 CTC 中观察到上皮细胞黏附分子、泛细胞角蛋白(CK)、E-钙黏蛋白、波形蛋白和 CK7 表达的异质性,可能解释了两种平台之间 CTC 数量的差异。
ISET 比 CellSearch 检测到更多的 CTC,并且提供了灵活的 CTC 特征分析,具有研究 CTC 生物学和开发用于胰腺癌患者管理的生物标志物的潜力。