Detection of Circulating Tumor Cells with a Novel Microfluidic System in Malignant Pleural Mesothelioma

Abstract

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. The CellSearch, only approved system for clinical use, fails to capture EpCAM‐negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC‐chip) in which any antibody to capture CTCs is conjugated. The CTC‐chip was coated with an antibody against podoplanin that is abundantly expressed on MPM. CTC‐detection performances were evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC‐chip showed superior CTC‐detection performances over CellSearch in experimental models (sensitivity, 63.3 ‐ 64.5% versus 0 ‐ 1.1%; P<0.001) and in clinical samples (CTC‐positivity, 68.8% versus 6.3%; P<0.001). A receiver operating characteristics (ROC) analysis showed that the CTC‐test provided a significant diagnostic performance in discrimination of un‐resectable disease from resectable disease (area under ROC curve, 0.851; P=0.003). The higher CTC‐count (≥2cells/mL) was significantly associated with a poor prognosis (P=0.030). The novel CTC‐chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM.

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