EpCAMlow Circulating Tumor Cells: Gold in the Waste.

Chiara Nicolazzo,Flavia Loreni,Cristina Raimondi,Angela Gradilone,Paola Gazzaniga

doi:10.1155/2019/1718920

Chiara Nicolazzo, Flavia Loreni + Show 3 more

Open Access

https://doi.org/10.1155/2019/1718920

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Journal: Disease markers	Publication Date: Sep 17, 2019
Citations: 20	License type: CC BY 4.0

Affiliation: Sapienza University of Rome

Abstract

The CellSearch® system which is still considered the gold standard for the enumeration of circulating tumor cells (CTC) utilizes antibodies against the epithelial cell adhesion molecule (EpCAM) for CTC enrichment. Recently, CTC discarded by the CellSearch® system due to their low EpCAM expression have been isolated and analyzed. We here sought to discuss technical and biological issues concerning the isolation and characterization of EpCAMlow CTC, highlighting the enormous potential of this subpopulation discarded by CellSearch®, which might instead reveal an unexpected clinical significance in tumor types where CTC enumeration has never been validated for prognostic and predictive purpose.

Highlights

The CellSearch® system (Menarini Silicon Biosystems, Castel Maggiore, BO, Italy) was placed on the market by Veridex Corporation (Warren, NJ) in 2004, and despite 15 years having passed, it still considered the gold standard for the enumeration of circulating tumor cells (CTC), the first and the only one cleared by the US FDA for monitoring of metastatic breast, colorectal, and prostate cancers [1].The CellSearch® system detects CTC from the whole blood of cancer patients through an immunomagnetic selection using a ferrofluid capture reagent
In the following years, it became clear that higher numbers of CTC can be detected using alternative, epithelial cell adhesion molecule (EpCAM)-independent methods, suggesting that a mixture of EpCAM-positive and EpCAM-negative tumor cells circulates in the blood [6]
We will discuss technical and biological issues concerning the isolation and characterization of CTC expressing no or low EpCAM, highlighting the enormous potential of this subpopulation discarded by the system, which might instead reveal an unexpected clinical significance in tumor types where CTC enumeration has never been validated for prognostic and predictive purpose

Summary

Introduction

The CellSearch® system (Menarini Silicon Biosystems, Castel Maggiore, BO, Italy) was placed on the market by Veridex Corporation (Warren, NJ) in 2004, and despite 15 years having passed, it still considered the gold standard for the enumeration of circulating tumor cells (CTC), the first and the only one cleared by the US FDA for monitoring of metastatic breast, colorectal, and prostate cancers [1]. The CellSearch® system detects CTC from the whole blood of cancer patients through an immunomagnetic selection using a ferrofluid capture reagent. This is a suspension of magnetic nanoparticles conjugated to a mouse monoclonal antibody recognizing the epithelial cell adhesion molecule (EpCAM) present on the surface of epithelial origin cells. In the following years, it became clear that higher numbers of CTC can be detected using alternative, EpCAM-independent methods, suggesting that a mixture of EpCAM-positive and EpCAM-negative tumor cells circulates in the blood [6]. We will discuss technical and biological issues concerning the isolation and characterization of CTC expressing no or low EpCAM, highlighting the enormous potential of this subpopulation discarded by the system, which might instead reveal an unexpected clinical significance in tumor types where CTC enumeration has never been validated for prognostic and predictive purpose

EpCAMhigh and EpCAMlow Circulating Tumor Cells

Findings

EpCAMlow CTC from a Clinical Perspective