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Open Access Highly Accessed Research

Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients

Andreia de Albuquerque1*, Ilja Kubisch2, Ulrich Stölzel2, Dominikus Ernst3, Joachim Boese-Landgraf3, Georg Breier4, Gudrun Stamminger5, Nikos Fersis6 and Sepp Kaul1

Author Affiliations

1 Department of Molecular Biology, Zentrum für Diagnostik am Klinikum Chemnitz, Flemmingstrasse 2, 09116, Chemnitz, Germany

2 Department of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany

3 Department of Surgery, Klinikum Chemnitz, Chemnitz, Germany

4 Department of Pathology, Technischen Universität Dresden, Dresden, Germany

5 Zentrum für Diagnostik, Chemnitz, Germany

6 Department of Gynecology, Klinikum Chemnitz, Chemnitz, Germany

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Journal of Translational Medicine 2012, 10:222  doi:10.1186/1479-5876-10-222

Published: 13 November 2012

Abstract

Objective

The aim of this study was to assess the prognostic and predictive values of circulating tumor cell (CTC) analysis in colorectal cancer patients.

Patients and methods

Presence of CTCs was evaluated in 60 colorectal cancer patients before systemic therapy - from which 33 patients were also evaluable for CTC analysis during the first 3 months of treatment - through immunomagnetic enrichment, using the antibodies BM7 and VU1D9 (targeting mucin 1 and EpCAM, respectively), followed by real-time RT-PCR analysis of the tumor-associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5.

Results

Patients were stratified into groups according to CTC detection (CTC negative, when all marker genes were negative; and CTC positive when at least one of the marker genes was positive). Patients with CTC positivity at baseline had a significant shorter median progression-free survival (median PFS 181.0 days; 95% CI 146.9-215.1) compared with patients with no CTCs (median PFS 329.0 days; 95% CI 299.6-358.4; Log-rank P < .0001). Moreover, a statistically significant correlation was also founded between CTC detection during treatment and radiographic findings at the 6 month staging. This correlation applied to CTC results before therapy (odds ratio (OR), 6.22), 1 to 4 weeks after beginning of treatment (OR, 5.50), 5 to 8 weeks after beginning of treatment (OR, 7.94) 9 to 12 weeks after beginning of treatment (OR, 14.00) and overall CTC fluctuation during the course of treatment (OR, 20.57).

Conclusion

The present study provides evidence of a strong correlation between CTC detection and radiographic disease progression in patients receiving chemotherapy for colorectal cancer. Our results suggest that in addition to the current prognostic factors, CTC analysis represent a potential complementary tool for prediction of colorectal cancer patients’ outcome. Moreover, the present test allows for molecular characterization of CTCs, which may be of relevance to the creation of personalized therapies.

Keywords:
Circulating tumor cells; Colorectal cancer; Reverse transcription real-time polymerase chain reaction