title: Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions.
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.
authors.affiliation: VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France.|Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, AP-HM, Marseille, France.|Cattedra di Malattie dell'Apparato Respiratorio, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Elisa
authors.initials: E
authors.lastname: Roca
authors.affiliation: VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France.|Hematology and Vascular Biology Department, CHU La Conception, APHM, Marseille, France.
authors.forename: Romaric
authors.initials: R
authors.lastname: Lacroix
authors.affiliation: R and T department, BioCytex, Marseille, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Judicone
authors.affiliation: Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, AP-HM, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Laroumagne
authors.affiliation: VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Robert
authors.affiliation: VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France.|Hematology and Vascular Biology Department, CHU La Conception, APHM, Marseille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cointe
authors.affiliation: R and T department, BioCytex, Marseille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Muller
authors.affiliation: AP-HM, Hôpital de la Timone, Service de Biologie Cellulaire, Marseille, France.|Aix-Marseille Université, INSERM, GMGF UMR_S910, Marseille, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Kaspi
authors.affiliation: AP-HM, Hôpital de la Timone, Service de Biologie Cellulaire, Marseille, France.|Aix-Marseille Université, INSERM, GMGF UMR_S910, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Roll
authors.affiliation: UMR-CBMN University of Bordeaux-CNRS-IPB, Pessac, France.
authors.forename: Alain R
authors.initials: AR
authors.lastname: Brisson
authors.affiliation: Cattedra di Malattie dell'Apparato Respiratorio, Università degli Studi di Brescia, Brescia, Italia.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tantucci
authors.affiliation: Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, Hôpital Nord, AP-HM, Marseille, France.|Aix-Marseille Université, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Astoul
authors.affiliation: VRCM, UMR-S1076, Aix-Marseille Université, INSERM, Faculté de Pharmacie, Marseille, France.|Hematology and Vascular Biology Department, CHU La Conception, APHM, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D055252:Cell-Derived Microparticles / Q000473:pathology / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D004797:Enzyme-Linked Immunosorbent Assay; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000503:physiopathology*; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: EpCAM; extracellular vesicles; microparticles; pleural effusion; pleural neoplasia