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Published in: Tumor Biology 4/2012

01-08-2012 | Research Article

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

Authors: 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

Published in: Tumor Biology | Issue 4/2012

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Abstract

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.
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMed
2.
go back to reference Nathoo N, Chahlavi A, Barnett GH, Toms SA. Pathobiology of brain metastases. J Clin Pathol. 2005;58:237–42.CrossRef Nathoo N, Chahlavi A, Barnett GH, Toms SA. Pathobiology of brain metastases. J Clin Pathol. 2005;58:237–42.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRef 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.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference Janssen-Heijnen ML, Coebergh JW. The changing epidemiology of lung cancer in Europe. Lung Cancer. 2003;41:245–58.CrossRef Janssen-Heijnen ML, Coebergh JW. The changing epidemiology of lung cancer in Europe. Lung Cancer. 2003;41:245–58.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference Tufman A, Huber RM. Biological markers in lung cancer: a clinician’s perspective. Cancer Biomark. 2010;6:123–35.CrossRef Tufman A, Huber RM. Biological markers in lung cancer: a clinician’s perspective. Cancer Biomark. 2010;6:123–35.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.PubMed 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.PubMed
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference Kuespert K, Pils S, Hauck CR. CEACAMs: their role in physiology and pathophysiology. Curr Opin Cell Biol. 2006;18:565–71.CrossRef Kuespert K, Pils S, Hauck CR. CEACAMs: their role in physiology and pathophysiology. Curr Opin Cell Biol. 2006;18:565–71.CrossRef
17.
go back to reference Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81.CrossRef Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81.CrossRef
18.
go back to reference Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta. 2001;310:173–86.CrossRef Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta. 2001;310:173–86.CrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.PubMed 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.PubMed
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer
Authors
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
Publication date
01-08-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0344-0

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