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.
Highlights
Malignant pleural effusion (MPE) is very common in cancer patients [1, 2] reflecting the dissemination of malignancy as well as advanced disease [3]
We investigated the presence of MPs in pleural fluids using highly sensitive flow cytometry
The detection of EpCAM+ MPs by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions
Summary
Malignant pleural effusion (MPE) is very common in cancer patients [1, 2] reflecting the dissemination of malignancy as well as advanced disease [3]. The capacity of EpCAM+ MPs to distinguish benign and MPE was evaluated by two methods : 1) high sensitive flow cytometry, performed directly on the pleural fluid and 2) ELISA for EpCAM antigen performed on the www.impactjournals.com/oncotarget Using ELISA test, the detection of EpCAM+ MPs was positive in 66% (29/44) of carcinoma pleurisies with 233 [42–713] pg/ml and in 3/27 with non-carcinoma malignant pleural effusions (mesothelioma) with a low concentration EpCAM (7 pg/ ml) (Figure 3B).
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