Cancer Science 2018 November 30 [Link]

Yoneda K, Kuwata T, Chikaishi Y, Mori M, Kanayama M, Takenaka M, Oka S, Hirai A, Imanishi N, Kuroda K, Ichiki Y, Ohnaga T, Tanaka F


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.