Tumor Biology

, Volume 33, Issue 4, pp 1065–1073 | Cite as

The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer

  • Dong-Soo Lee
  • Yeon-Sil Kim
  • So-Lyoung Jung
  • Kyo-Young Lee
  • Jin-Hyoung Kang
  • Sarah Park
  • Young-Kyoon Kim
  • Ie-Ryung Yoo
  • Byung-Ock Choi
  • Hong-Seok Jang
  • Sei-Chul Yoon
Research Article


Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1–3) and high total metastatic score group (score 4–7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.


Non-small cell lung carcinoma Carcinoembryonic antigen Neoplasm metastasis Brain Biological marker 



This study was advised by the Catholic Research Coordinating Center and supported by a grant from the Korea Health 21 R&D Project (A070001), Ministry of Health and Welfare, Republic of Korea.

Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Nathoo N, Chahlavi A, Barnett GH, Toms SA. Pathobiology of brain metastases. J Clin Pathol. 2005;58:237–42.PubMedCrossRefGoogle Scholar
  3. 3.
    Meert AP, Paesmans M, Berghmans T, Martin B, Mascaux C, Vallot F, et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer. 2001;1:5.PubMedCrossRefGoogle Scholar
  4. 4.
    Gore EM, Bae K, Wong SJ, Sun A, Bonner JA, Schild SE, et al. Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol. 2011;29:272–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Anzalone N, Gerevini S, Scotti R, Vezzulli P, Picozzi P. Detection of cerebral metastases on magnetic resonance imaging: intraindividual comparison of gadobutrol with gadopentetate dimeglumine. Acta Radiol. 2009;50:933–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Janssen-Heijnen ML, Coebergh JW. The changing epidemiology of lung cancer in Europe. Lung Cancer. 2003;41:245–58.PubMedCrossRefGoogle Scholar
  7. 7.
    Travis WD, Lubin J, Ries L, Devesa S. United States lung carcinoma incidence trends: declining for most histologic types among males, increasing among females. Cancer. 1996;77:2464–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Tufman A, Huber RM. Biological markers in lung cancer: a clinician’s perspective. Cancer Biomark. 2010;6:123–35.PubMedGoogle Scholar
  9. 9.
    Barak V, Holdenrieder S, Nisman B, Stieber P. Relevance of circulating biomarkers for the therapy monitoring and follow-up investigations in patients with non-small cell lung cancer. Cancer Biomark. 2010;6:191–6.PubMedGoogle Scholar
  10. 10.
    Tie J, Lipton L, Desai J, Gibbs P, Jorissen RN, Christie M, et al. KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res. 2011;17:1122–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Saad AG, Yeap BY, Thunnissen FB, Pinkus GS, Pinkus JL, Loda M, et al. Immunohistochemical markers associated with brain metastases in patients with non-small cell lung carcinoma. Cancer. 2008;113:2129–38.PubMedCrossRefGoogle Scholar
  12. 12.
    Marchi N, Mazzone P, Fazio V, Mekhail T, Masaryk T, Janigro D. Proapolipoprotein A1: a serum marker of brain metastases in lung cancer patients. Cancer. 2008;112:1313–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Hsu WH, Huang CS, Hsu HS, Huang WJ, Lee HC, Huang BS, et al. Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non-small-cell lung cancer. Ann Thorac Surg. 2007;83:419–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Ishiguro F, Fukui T, Mori S, Katayama T, Sakakura N, Hatooka S, et al. Serum carcinoembryonic antigen level as a surrogate marker for the evaluation of tumor response to chemotherapy in non-small cell lung cancer. Ann Thorac Cardiovasc Surg. 2010;16:242–7.PubMedGoogle Scholar
  15. 15.
    Arrieta O, Saavedra-Perez D, Kuri R, Aviles-Salas A, Martinez L, Mendoza-Posada D, et al. Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis. BMC Cancer. 2009;9:119.PubMedCrossRefGoogle Scholar
  16. 16.
    Kuespert K, Pils S, Hauck CR. CEACAMs: their role in physiology and pathophysiology. Curr Opin Cell Biol. 2006;18:565–71.PubMedCrossRefGoogle Scholar
  17. 17.
    Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81.PubMedCrossRefGoogle Scholar
  18. 18.
    Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta. 2001;310:173–86.PubMedCrossRefGoogle Scholar
  19. 19.
    Kang SJ, Kim KS, Ha YS, Huh SY, Lee JH, Kim JK, et al. Diagnostic value of cerebrospinal fluid level of carcinoembryonic antigen in patients with leptomeningeal carcinomatous metastasis. J Clin Neurol. 2010;6:33–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Wu SG, Yang CH, Yu CJ, Lee JH, Hsu YC, Chang YL, et al. Good response to pemetrexed in patients of lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Lung Cancer. 2011;72:333–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Molina R, Auge JM, Escudero JM, Marrades R, Viñolas N, Carcereny E, et al. Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE. Tumour Biol. 2008;29:371–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Nisman B, Amir G, Lafair J, Heching N, Lyass O, Peretz T, et al. Prognostic value of CYFRA 21-1, TPS and CEA in different histologic types of non-small cell lung cancer. Anticancer Res. 1999;19:3549–52.PubMedGoogle Scholar
  23. 23.
    Blumenthal RD, Hansen HJ, Goldenberg DM. Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen). Cancer Res. 2005;65:8809–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Cases A, Filella X, Molina R, Ballesta AM, Lopez-Pedret J, Revert L. Tumor markers in chronic renal failure and hemodialysis patients. Nephron. 1991;57:183–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Okada M, Nishio W, Sakamoto T, Uchino K, Yuki T, Nakagawa A, et al. Effect of histologic type and smoking status on interpretation of serum carcinoembryonic antigen value in non-small cell lung carcinoma. Ann Thorac Surg. 2004;78:1004–9. discussion 1009-10.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Dong-Soo Lee
    • 1
  • Yeon-Sil Kim
    • 1
  • So-Lyoung Jung
    • 2
  • Kyo-Young Lee
    • 3
  • Jin-Hyoung Kang
    • 4
  • Sarah Park
    • 4
  • Young-Kyoon Kim
    • 5
  • Ie-Ryung Yoo
    • 6
  • Byung-Ock Choi
    • 1
  • Hong-Seok Jang
    • 1
  • Sei-Chul Yoon
    • 1
  1. 1.Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaSeocho-guRepublic of Korea
  2. 2.Department of Radiology, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  3. 3.Department of Pathology, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  4. 4.Department of Medical Oncology, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  5. 5.Department of Internal Medicine, Division of Pulmonology, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  6. 6.Department of Nuclear Medicine, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea

Personalised recommendations