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Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells

Oncogene volume 21, pages 7817–7823 (2002)Cite this article

Abstract

Quantification of circulating cancer cells in whole blood samples by real time quantitative RT–PCR might be of clinical value for monitoring therapeutic effectiveness. In colon cancer patients, carcinoembrynic antigen (CEA) and cytokeratin 20 (CK20) have been frequently used for RT–PCR based tumor cell detection, but the specificity in particular for CEA has been questioned. In this study, we compared real-time RT–PCR for CEA and CK20 and analysed patients with metastatic disease (n=32) and healthy volunteers (n=17). CK20 mean values were elevated in cancer patients (P<0.001) and defined a subgroup (38%) who showed CK20 levels at least 100-fold above the highest value of the healthy control group. In contrast, only two cancer patients (6%) showed elevated CEA levels. Samples of the healthy control group showed exclusively a CEA-PCR product of 79°C melting temperature. Thirty per cent of the colon cancer patients showed an additional product of 82°C melting temperature. The 82°C product was identical with the amplification product of CEA-cDNA and cDNA from different colon cancer cell lines. Colon cancer cells were spiked into normal blood in 10-fold dilutions that resulted in a dose dependent shift of the melt curve from 79°C to the 82°C. Sequencing of the PCR products showed that white blood cells express a splice variant of CEA, which hinders detection of tumor cell cDNA in whole blood samples. Our findings have implications for the use of CEA as a diagnostic molecule (e.g. by RT–PCR). The discovery of a physiologically expressed CEA splice variant might lead to a better understanding of the biological function of CEA and its family members.

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Acknowledgements

Dan P Hartman, Department of Pathology, Georgetown University Medical Center and Jeff M Smith, Bio-Rad Laboratories, for numerous helpful suggestions This work was supported by a grant of the National Institute of Health/National Cancer Institute (#R01-CA088972), and Lombardi Cancer Research Center Core Facility, U.S. Public Health Service Grant 2P30-CA-51008

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  1. Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, 20007, DC, USA

    Regina Hampton, Mignon Walker, John Marshall & Hartmut Juhl

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  1. Regina Hampton
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Correspondence to Hartmut Juhl.

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Hampton, R., Walker, M., Marshall, J. et al. Differential expression of carcinoembryonic antigen (CEA) splice variants in whole blood of colon cancer patients and healthy volunteers: implication for the detection of circulating colon cancer cells. Oncogene 21, 7817–7823 (2002). https://doi.org/10.1038/sj.onc.1205906

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