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 Roca1,2,3, Romaric Lacroix1,4, Coralie Judicone5, Sophie Laroumagne2, Stéphane Robert1, Sylvie Cointe1,4, Alexandre Muller5, Elise Kaspi6,7, Patrice Roll6,7, Alain R. Brisson8, Claudio Tantucci3, Philippe Astoul2,9,*, Françoise Dignat-George1,4,*
1VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France
2Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, AP-HM, Marseille, France
3Cattedra di Malattie dell'Apparato Respiratorio, Università degli Studi di Brescia, Brescia, Italia
4Hematology and Vascular Biology Department, CHU La Conception, APHM, Marseille, France
5R and T department, BioCytex, Marseille, France
6AP-HM, Hôpital de la Timone, Service de Biologie Cellulaire, Marseille, France
7Aix-Marseille Université, INSERM, GMGF UMR_S910, Marseille, France
8UMR-CBMN University of Bordeaux-CNRS-IPB, Pessac, France
9Aix-Marseille Université, Marseille, France
*These authors contributed equally to this work
Romaric Lacroix, e-mail: firstname.lastname@example.org
Keywords: extracellular vesicles, microparticles, pleural effusion, pleural neoplasia, EpCAM
Received: August 13, 2015 Accepted: November 16, 2015 Published: December 12, 2015
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.
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