Use of Circulating Tumor Cell Technology (CELLSEARCH) for the Diagnosis of Malignant Pleural Effusions

Abstract

Rationale: Cytological analysis of pleural effusions (PEs) has a sensitivity of approximately 60%. We hypothesized that the CELLSEARCH technology (Janssen Research and Development, Huntingdon Valley, PA) currently used to detect circulating tumor cells could be adapted for the identification of tumor cells in PEs.Methods: This was a single-center, prospective, observational study. Pleural fluid from subjects with undiagnosed PEs were analyzed by CELLSEARCH technology, which uses an epithelial cell adhesion molecule antibody-based capture system/cytokeratin antibodies to identify tumor cells. Subjects were prospectively monitored by periodic chart review to determine the etiology of the PE. Measurements and Main Results:One hundred thirty-two subjects were analyzed. A malignant etiology was established in 81 subjects. The median number of "positive" pleural epithelial cells (PECs) detected per milliliter of pleural fluid was 6 in the benign group. The number of PECs was 52 in the malignant nonepithelial group (NS) and 526 in the malignant epithelial group (P , 0.001). Unlike blood, there was a baseline number of "positive" cells in benign pleural fluids; however, any cutoff greater than 852 positive cells/ml had 100% specificity. The area under the receiver operating characteristic curve was 0.86. Nine percent of our cancer cases had high numbers of PECs (.280/ml) but a negative or nondefinitive cancer diagnosis by cytology. Conclusions:The pleural CELLSEARCH assay may serve as a valuable addition to traditional cytology and provide useful information regarding the diagnosis of malignant effusions. Major advantages include that it is well standardized, relatively inexpensive, has a rapid turnaround, and is easily available. Our data support the conduct of additional studies of this approach to assist in the diagnosis of malignant PEs.

Improved diagnosis and prognostication of patients with pleural malignant mesothelioma using biomarkers in pleural effusions and peripheral blood samples – a short report

“…Using this latter technique, however, we noted that a vast number of non-mesothelioma pleural effusions contained relatively high numbers of cells meeting the criteria for tumor cells. This limited specificity of the CellSearch system is in accordance with observations reported by Lustgarten and colleagues [ 27 ]. This group attempted to improve the diagnosis of malignant pleural effusions by the CellSearch system using EpCAM to enrich for CTCs.…”

A Multiplexed Cytokeratin Analysis Using Targeted Mass Spectrometry Reveals Specific Profiles in Cancer-Related Pleural Effusions

“…For comparison, our best single marker had an AUC of 0.83 compared with that of Chen et al whose best single marker had an AUC of 0.76 in such a grouping [26] . Our results are also on par with the FDA-approved test (CELLSEARCH) which partly uses CK antibodies [51] as it was used to improve on cytology assessment, differentiating malignant from benign PEs with an AUC of 0.86 and a sensitivity of 78% and specificity of 86% [52] . We had insufficient clinical data to exclude paramalignant PEs, and possibly, our classifier could score even higher in a malignant-centric approach.…”

Several circulating miRNAs related to hyperlipidemia and atherosclerotic cardiovascular diseases

“…Previous studies on serum miRNA, such as acute myocardial infarction, coronary heart disease, and cerebral stroke, etc. [29–31], have proved that miRNA-933 could not only exist stably in the peripheral blood but also possessed significant differences when compared with control groups. However, few of these studies conducted further research on the correlation between circulating miRNA-933 and hyperlipidemia.…”