Skip to main content
SpringerLink
Log in

The Association of Serum Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Thymidine Kinase, and Tissue Polypeptide Specific Antigen with Outcomes of Patients with Metastatic Colorectal Cancer Treated with Bevacizumab: a Retrospective Study

  • Original Research
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

The aim of our retrospective study was to analyze the association of selected tumor markers (TMs) including serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase, and tissue polypeptide specific antigen with outcomes in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab. There is an increasing body of evidence from retrospective/observational studies that some serum TMs may be predictive of effect of targeted therapies in mCRC. In our study, the cohort included 152 patients treated with bevacizumab-based therapy between years 2005 and 2014 at Department of Oncology and Radiotherapy, Medical School and Teaching Hospital Pilsen. Serum samples for measurement of TMs were collected within 1 month before the initiation of bevacizumab-based treatment. In multivariate Cox analysis that included serum tumor markers and clinical baseline parameters, the number of metastatic sites (hazard ratio [HR] = 2.00, p = 0.001) and CEA levels (HR = 2.80, p < 0.001) were significantly associated with progression-free survival, whereas CA 19-9 levels (HR = 2.25, p = 0.008) were the only studied parameter associated with overall survival. Quantification of serum CEA and CA 19-9 is simple and readily available, and their candidate prognostic importance in the setting of antiangiogenesis therapy deserves to be studied in prospective trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–81

    Article  CAS  PubMed  Google Scholar 

  3. Yamashita K, Watanabe M (2009) Clinical significance of tumor markers and an emerging perspective on colorectal cancer. Cancer Sci 100:195–9

    Article  CAS  PubMed  Google Scholar 

  4. Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L et al (2014) Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer 134:2513–22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP (1989) Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 57:327–34

    Article  CAS  PubMed  Google Scholar 

  6. Screaton RA, Penn LZ, Stanners CP (1997) Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation. J Cell Biol 137:939–52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Bramswig KH, Poettler M, Unseld M, Wrba F, Uhrin P, Zimmermann W et al (2013) Soluble carcinoembryonic antigen activates endothelial cells and tumor angiogenesis. Cancer Res 73:6584–96

    Article  CAS  PubMed  Google Scholar 

  8. Ballehaninna UK, Chamberlain RS (2012) The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol 3:105–19

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Zhou J, He E, Skog S (2013) The proliferation marker thymidine kinase 1 in clinical use. Mol Clin Oncol 1:18–28

    PubMed Central  PubMed  Google Scholar 

  10. Rydlander L, Ziegler E, Bergman T, Schöberl E, Steiner G, Bergman AC et al (1996) Molecular characterization of a tissue-polypeptide-specific-antigen epitope and its relationship to human cytokeratin 18. Eur J Biochem 241:309–14

    Article  CAS  PubMed  Google Scholar 

  11. Bodenmuller H (1995) The biochemistry of CYFRA 21-1 and other cytokeratin tests. Scand J Clin Lab Investig Suppl 221:60–6

    Article  CAS  Google Scholar 

  12. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumours. European organization for research and treatment of cancer, national cancer institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 3:205–16

    Article  Google Scholar 

  13. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 250:2335–42

    Article  Google Scholar 

  14. Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival in patients with metastatic colorectal cancer. J Clin Oncol 23:3706–12

    Article  CAS  PubMed  Google Scholar 

  15. Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–9

    Article  CAS  PubMed  Google Scholar 

  16. Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM et al (2009) Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 14:862–70

    Article  CAS  PubMed  Google Scholar 

  17. Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M et al (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 20:1842–7

    Article  PubMed  Google Scholar 

  18. Goede V, Coutelle O, Neuneier J, Reinacher-Schick A, Schnell R, Koslowsky TC et al (2010) Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy. Br J Cancer 103:1407–14

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ (2013) Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 31:1219–30

    Article  CAS  PubMed  Google Scholar 

  20. Zhang W, Azuma M, Lurje G, Gordon MA, Yang D, Pohl A et al (2010) Molecular predictors of combination targeted therapies (cetuximab, bevacizumab) in irinotecan-refractory colorectal cancer (BOND-2 study). Anticancer Res 30:4209–17

    CAS  PubMed  Google Scholar 

  21. Huh JW, Oh BR, Kim HR, Kim YJ (2010) Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer. J Surg Oncol 101:396–400

    PubMed  Google Scholar 

  22. Sun LC, Chu KS, Cheng SC, Lu CY, Kuo CH, Hsieh JS et al (2009) Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment. BMC Cancer 9:288

    Article  PubMed Central  PubMed  Google Scholar 

  23. Park IJ, Choi GS, Lim KH, Kang BM, Jun SH (2009) Serum carcinoembryonic antigen monitoring after curative resection for colorectal cancer: clinical signifi- cance of the preoperative level. Ann Surg Oncol 16:3087–93

    Article  PubMed  Google Scholar 

  24. Peng Y, Wang L, Gu J (2013) Elevated preoperative carcinoembryonic antigen (CEA) and Ki67 is predictor of decreased survival in IIA stage colon cancer. World J Surg 37:208–13

    Article  PubMed  Google Scholar 

  25. Harrison LE, Guillem JG, Paty P, Cohen AM (1997) Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients. J Am Coll Surg 185:55–9

    Article  CAS  PubMed  Google Scholar 

  26. Yuste AL, Aparicio J, Segura A, López-Tendero P, Gironés R, Pérez-Fidalgo JA et al (2003) Analysis of clinical prognostic factors for survival and time to progression in patients with metastatic colorectal cancer treated with 5-fluorouracil-based chemotherapy. Clin Colorectal Cancer 2:231–4

    Article  PubMed  Google Scholar 

  27. Wang WS, Lin JK, Chiou TJ, Liu JH, Fan FS, Yen CC et al (2002) CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer. Hepatogastroenterology 49:160–4

    PubMed  Google Scholar 

  28. Aggarwal C, Meropol NJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD et al (2013) Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer. Ann Oncol 4:420–8

    Article  Google Scholar 

  29. Prager GW, Braemswig KH, Martel A, Unseld M, Heinze G, Brodowicz T et al (2014) Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer. Cancer Sci 105:996–1001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Formica V, Massara MC, Portarena I, Fiaschetti V, Grenga I, Del Vecchio Blanco G et al (2009) Role of CA19.9 in predicting bevacizumab efficacy for metastatic colorectal cancer patients. Cancer Biomark 5:167–75

    CAS  PubMed  Google Scholar 

  31. Narita Y, Taniguchi H, Komori A, Nitta S, Yamaguchi K, Kondo C et al (2014) CA19-9 level as a prognostic and predictive factor of bevacizumab efficacy in metastatic colorectal cancer patients undergoing oxaliplatin-based chemotherapy. Cancer Chemother Pharmacol 73:409–16

    Article  CAS  PubMed  Google Scholar 

  32. Brockenbrough JS, Morihara JK, Hawes SE, Stern JE, Rasey JS, Wiens LW et al (2009) Thymidine kinase 1 and thymidine phosphorylase expression in non-small-cell lung carcinoma in relation to angiogenesis and proliferation. J Histochem Cytochem 57:1087–97

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Svobodova S, Topolcan O, Holubec L, Treska V, Sutnar A, Rupert K et al (2007) Prognostic importance of thymidine kinase in colorectal and breast cancer. Anticancer Res 27:1907–9

    CAS  PubMed  Google Scholar 

  34. Treska V, Topolcan O, Stanislav K, Liska V, Holubec L (2009) Preoperative tumor markers as prognostic factors of colorectal liver metastases. Hepatogastroenterology 56:317–20

    CAS  PubMed  Google Scholar 

  35. Glimelius B, Hoffman K, Einarsson R, Pählman L, Graf W (1996) Monitoring palliative chemotherapy in advanced gastrointestinal cancer using serial tissue polypeptide specific antigen (TPS) measurements. Acta Oncol 35:141–8

    Article  CAS  PubMed  Google Scholar 

  36. Kornek G, Schenk T, Raderer M, Djavarnmad M, Scheithauer W (1995) Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment response of patients with gastrointestinal tumours. Br J Cancer 71:182–5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Berglund A, Molin D, Larsson A, Einarsson R, Glimelius B (2002) Tumour markers as early predictors of response to chemotherapy in advanced colorectal carcinoma. Ann Oncol 13:1430–7

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank all patients voluntarily taking part in the observational, population-based registry CORECT. This study is supported by the Ministry of Health, Czech Republic—conceptual development of research organization Faculty Hospital in Pilsen—FNPl, 00669806 and by the project CZ.1.05/2.1.00/03.0076 from the European Regional Development Fund.

Conflict of Interest

JF has received honoraria from Astra Zeneca, Roche, and Novartis for consultations and lectures unrelated to this project. TB has received honoraria from Roche for consultations and lectures unrelated to this project. OF, VMM, LH, JK, ZB, VL, and OT declare that they have no actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations that could inappropriately influence this work.

Author information

Authors and Affiliations

  1. Department of Oncology and Radiotherapy, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, alej Svobody 80, 304 60, Pilsen, Czech Republic

    Ondrej Fiala, Jindrich Finek, Vit Martin Matejka, Lubos Holubec & Jana Kulhankova

  2. Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic

    Ondrej Fiala, Lubos Holubec & Vaclav Liska

  3. Department of Oncology and First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic

    Tomas Buchler

  4. Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic

    Zbynek Bortlicek

  5. Department of Surgery, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic

    Vaclav Liska

  6. Department of Nuclear Medicine, Medical School and Teaching Hospital in Pilsen, Charles University in Prague, Pilsen, Czech Republic

    Ondrej Topolcan

Authors
  1. Ondrej Fiala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jindrich Finek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomas Buchler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vit Martin Matejka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lubos Holubec
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jana Kulhankova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zbynek Bortlicek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vaclav Liska
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ondrej Topolcan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ondrej Fiala.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fiala, O., Finek, J., Buchler, T. et al. The Association of Serum Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Thymidine Kinase, and Tissue Polypeptide Specific Antigen with Outcomes of Patients with Metastatic Colorectal Cancer Treated with Bevacizumab: a Retrospective Study. Targ Oncol 10, 549–555 (2015). https://doi.org/10.1007/s11523-015-0365-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-015-0365-x

Keywords

Search

Navigation