Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions

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// Elisa Roca 1, 2, 3 , Romaric Lacroix 1, 4 , Coralie Judicone 5 , Sophie Laroumagne 2 , Stéphane Robert 1 , Sylvie Cointe 1, 4 , Alexandre Muller 5 , Elise Kaspi 6, 7 , Patrice Roll 6, 7 , Alain R. Brisson 8 , Claudio Tantucci 3 , Philippe Astoul 2, 9, * , Françoise Dignat-George 1, 4, * 1 VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France 2 Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, AP-HM, Marseille, France 3 Cattedra di Malattie dell'Apparato Respiratorio, Università degli Studi di Brescia, Brescia, Italia 4 Hematology and Vascular Biology Department, CHU La Conception, APHM, Marseille, France 5 R and T department, BioCytex, Marseille, France 6 AP-HM, Hôpital de la Timone, Service de Biologie Cellulaire, Marseille, France 7 Aix-Marseille Université, INSERM, GMGF UMR_S910, Marseille, France 8 UMR-CBMN University of Bordeaux-CNRS-IPB, Pessac, France 9 Aix-Marseille Université, Marseille, France * These authors contributed equally to this work Correspondence to: Romaric Lacroix, e-mail: romaric.lacroix@univ-amu.fr Keywords: extracellular vesicles, microparticles, pleural effusion, pleural neoplasia, EpCAM Received: August 13, 2015 Accepted: November 16, 2015 Published: December 12, 2015 ABSTRACT Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign ( n = 14) and malignant ( n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions.