A Microfluidic, Multi-Antibody Cell Capture Method to Evaluate Tumor Cells in Cerebrospinal Fluid in Patients With Suspected Leptomeningeal Metastases.

Nathan T Sweed, Hao-Ching Hsiao, Barbara Blouw, Tony J Pircher, Deanna Fisher, Katrina Rose Naluz, Julie Ann Mayer, Michael C Dugan, Akanksha Sharma, Jose Carrillo, Santosh Kesari
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Abstract

Context.—: Leptomeningeal disease (LMD) is a clinical sequela of central nervous system metastasis involving the cerebrospinal fluid (CSF), often seen in late-stage solid tumors. It has a grave prognosis without urgent treatment. Standard of care methodologies to diagnose LMD include CSF cytology, magnetic resonance imaging, and clinical evaluation. These methods offer limited sensitivity and specificity for the evaluation of LMD. Here, we describe the analytic performance characteristics of a microfluidic-based tumor cell enrichment and detection assay optimized to detect epithelial cells in CSF using both contrived samples as well as CSF from patients having suspected or confirmed LMD from carcinomas.

Objective.—: To demonstrate the feasibility of using a microfluidic, multi-antibody cell capture assay to identify and quantify tumor cells in CSF.

Design.—: An artificial CSF solution was spiked with 34 different human carcinoma cell lines at different concentrations and assayed for the ability to detect tumor cells to assess analytic accuracy. Two cell lines were selected to assess linearity, intra-assay precision, interinstrument precision, and sample stability. Clinical verification was performed on 65 CSF specimens from patients. Parameters assessed included the number of tumor cells, coefficient of variation percentage, and percentage of tumor cell capture (TCC).

Results.—: Among contrived samples, average tumor cell capture ranged from 50% to 82% (261 of 522; 436 of 531), and coefficients of variation ranged from 7% to 67%. The cell capture assay demonstrated a sensitivity of 92% and a specificity of 95% among clinical samples.

Conclusions.—: This assay demonstrated the ability to detect and enumerate epithelial cells in contrived and clinical specimens in an accurate and reproducible fashion. The use of cell capture assays in CSF may be useful as a sensitive test for the diagnosis and longitudinal monitoring of LMD from solid tumors.

用微流体多抗体细胞捕获法评估疑似脑膜转移患者脑脊液中的肿瘤细胞
背景脑膜病(LMD)是中枢神经系统转移累及脑脊液(CSF)的临床后遗症,常见于晚期实体瘤。如不紧急治疗,预后严重。诊断 LMD 的标准方法包括脑脊液细胞学检查、磁共振成像和临床评估。这些方法对评估 LMD 的灵敏度和特异性都很有限。在此,我们描述了一种基于微流控的肿瘤细胞富集和检测分析法的分析性能特点,该分析法经过优化,可使用假样本以及疑似或确诊为 LMD 癌症患者的 CSF 来检测 CSF 中的上皮细胞:证明使用微流控、多抗体细胞捕获检测法识别和量化 CSF 中肿瘤细胞的可行性:在人工 CSF 溶液中添加 34 种不同浓度的人类癌细胞株,并检测其检测肿瘤细胞的能力,以评估分析的准确性。选择两种细胞系来评估线性度、测定内精密度、仪器间精密度和样品稳定性。对 65 份患者 CSF 标本进行了临床验证。评估参数包括肿瘤细胞数量、变异系数百分比和肿瘤细胞捕获百分比(TCC):在伪造样本中,肿瘤细胞平均捕获率为 50%至 82%(522 份样本中的 261 份;531 份样本中的 436 份),变异系数为 7%至 67%。在临床样本中,细胞捕获测定的灵敏度为 92%,特异性为 95%:这种检测方法能够准确、可重复地检测和计数人造样本和临床样本中的上皮细胞。在 CSF 中使用细胞捕获检测法可作为诊断和纵向监测实体瘤 LMD 的灵敏检测方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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