Article | Published:

Molecular Diagnostics

Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome

British Journal of Cancervolume 118pages16091616 (2018) | Download Citation

Abstract

Background

Mutation status of RAS and BRAF, as well as serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are biomarkers used in clinical management of patients with gastrointestinal cancers. This study aimed to examine the prognostic role of these biomarkers in a patient population that started first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC) in the NORDIC-VII study.

Methods

CEA and CA 19-9 were measured in serum samples from 545 patients obtained before the start of chemotherapy. Four hundred and ninety-four patients had detectable levels of carbohydrate antigen 19-9 (CA 19-9). RAS (exons 2–4) and BRAF (V600E) mutation status were available from 440 patients. Overall survival (OS) was estimated in patient groups defined by serum CEA or CA 19-9 levels using cut-off values of 5 µg/L and 35 kU/L, respectively, in the total population and in subgroups according to RAS and BRAF mutation status.

Results

For both CEA and CA 19-9, elevated serum levels were associated with reduced OS in adjusted analyses which included RAS and BRAF mutation status, baseline World Health Organization performance status, and levels of alkaline phosphatase and C-reactive protein. The negative prognostic information provided by an elevated CA 19-9 level was particularly marked in patients with BRAF mutation (hazard ratio = 4.35, interaction P = 0.003, in an adjusted model for OS).

Conclusions

High baseline serum concentrations of CEA and CA 19-9 provide independent information of impaired prognosis in mCRC. In patients with BRAF-mutant tumours, elevated serum CA 19-9 may identify a subgroup with highly aggressive disease and could contribute to improving therapeutic decisions.

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Acknowledgements

We thank the patients and their families and the investigators who participated in the NORDIC-VII study. This work was supported by the Norwegian Cancer Society, the Swedish Cancer Society and by a generous financial support from the Raabe family. The NORDIC-VII study was supported by Merck KGaA, Darmstadt, Germany and Sanofi, Oslo, Norway.

Author information

Affiliations

  1. Department of Oncology, Oslo University Hospital, Oslo, Norway

    • Maria Thomsen
    • , Kjell Magne Tveit
    •  & Tormod Kyrre Guren
  2. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

    • Maria Thomsen
    •  & Kjell Magne Tveit
  3. Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway

    • Eva Skovlund
  4. Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway

    • Halfdan Sorbye
  5. Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

    • Nils Bolstad
    •  & Kjell Johannes Nustad
  6. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

    • Bengt Glimelius
  7. Department of Oncology, Odense University Hospital, Odense, Denmark

    • Per Pfeiffer
  8. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

    • Per Pfeiffer
  9. Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

    • Elin H. Kure
  10. Departments of Oncology and Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    • Julia S. Johansen
  11. K.G.Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway

    • Kjell Magne Tveit
    •  & Tormod Kyrre Guren
  12. Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

    • Thoralf Christoffersen

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Contributions

Study design: M.T., E.S., H.S., K.M.T., T.C., T.K.G.; provision of study materials or patients: H.S., N.B., K.J.N., B.G., P.P., E.H.K., J.S.J., K.M.T., T.K.G.; data analysis and interpretation: M.T., E.S., H.S., N.B., K.J.N., K.M.T., T.C., T.K.G.; manuscript writing: all authors.

Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

The NORDIC-VII study (http://clinicaltrials.gov/show/NCT00145314) was approved by the National Ethics Committees and governmental authorities in each country and conducted in accordance with the Declaration of Helsinki. Prognostic biomarker substudies were part of the protocol. All patients gave written informed consent to participate in the study.

Availability of data and material

The datasets generated during and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Corresponding author

Correspondence to Tormod Kyrre Guren.

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DOI

https://doi.org/10.1038/s41416-018-0115-9