Abstract

Enumeration of circulating tumor cells (CTCs) by the CellSearch system provides prognostic information in metastatic colorectal cancer, regardless of metastatic site. We found that CTCs generally represent <1% of observed events with CellSearch analysis and adapted scoring criteria to classify other peripheral blood events. Examination of twenty two metastatic colorectal cancer patients' blood revealed that patients with high CEA or liver metastases, but not lung or distant lymph node metastases, possessed significant numbers of apoptotic CTCs prior to treatment initiation by Fischer's exact test. Six out of eleven patients with liver metastasis possessed apoptotic CTCs whereas one of nine patients with other metastases had measurable apoptotic CTCs. An elevated CTC number was not necessarily associated with apoptotic CTCs or CTC debris by Spearman's correlation, suggesting the metastatic site rather than CTCs per se as contributing to the origin of these events.

Highlights

  • The detection of metastatic cells in the blood (circulating tumor cells (CTCs)) as a non-invasive window to monitor disease progression and prognosis as well as provide disease-specific information to aid in therapeutic stratification is paramount

  • To evaluate peripheral blood events other than CTCs, we first established a criteria for scoring general categories of events detected on the CellSearch system as one of the following: CTC, apoptotic CTC, CTC debris, debris, or leukocyte

  • Relationships between peripheral blood events and baseline CEA or metastatic sites We examined the relationships between peripheral blood events and carcinoembryonic antigen (CEA), which is one of the most commonly implemented and established prognostic markers in colorectal cancer

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Summary

Introduction

The detection of metastatic cells in the blood (circulating tumor cells (CTCs)) as a non-invasive window to monitor disease progression and prognosis as well as provide disease-specific information to aid in therapeutic stratification is paramount. A number of technologies have emerged to compete with the CellSearch system following its approval by the FDA, including techniques that detect circulating nucleic acids or filter tumor cells based on size or electrostatic properties rather than relying on epithelial cell adhesion molecule (EpCAM) expression [4]. The latter is especially important as it allows for the capture of live cells. There is an increasing appreciation for the involvement of epithelial-mesenchymal transition (EMT) in CTCs [5, 6], though the requisite loss of EpCAM expression in EMT and CTCs remains unclear

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