Advertisement

Nuclear Medicine and Molecular Imaging

, Volume 47, Issue 3, pp 181–187 | Cite as

Clinical Usefulness of Serum CYFRA 21–1 in Patients with Colorectal Cancer

  • Jai Hyuen Lee
Original Article

Abstract

Purpose

Among diverse tumor markers, pretreatment evaluation and follow-up detection of recurrence in colorectal cancer are generally evaluated by serum carcinoembryonic antigen (CEA) levels. However, there have been some reports about the low accuracy and high false-positive results of CEA in colorectal cancer. We investigated the clinical utilities of CYFRA 21–1 by comparing CEA and cancer antigen 19–9 (CA 19–9) in pretreatment and recurrent colorectal cancer.

Methods

Using a solid-phase immunoradiometric assay, serum levels of CYFRA 21–1, CEA and CA 19–9 were analyzed in 132 patients with primary colorectal cancer, 124 healthy controls, 104 patients with benign colorectal disease and 19 patients with recurrent colorectal cancer. We determined three different cutoff values to evaluate the sensitivity of diagnostic performance in pretreatment and recurrent colorectal cancer.

Results

CYFRA 21–1 (≥ 1.13 ng/ml) had a sensitivity of 47 %, compared with 37 % for CEA (≥ 3.05 ng/ml) and 32.6 % for CA 19–9 (≥ 23.1 ng/ml) in the initial staging of primary colorectal cancer. Using different cutoff values, CYFRA 21–1 showed higher sensitivity for pretreatment colorectal cancer than CEA and CA 19–9 in adenocarcinoma and adenosquamous carcinoma of this study. A mildly significant correlative relationship was noted between Dukes’ stages and three tumor markers (p < 0.01). The areas under the receiver operating characteristic curves of CYFRA 21–1, CEA and CA 19–9 were 0.81 ± 0.03, 0.74 ± 0.03 and 0.62 ± 0.04, respectively, for discriminating colorectal cancer patients from patients with benign colorectal disease. In addition, CYFRA 21–1 was determined as the most sensitive tumor marker for evaluating recurrent colorectal cancer for all cutoff values.

Conclusion

This study showed that CYFRA 21–1 could be a useful and dependable tumor marker for pretreatment and recurrent colorectal cancer. Further prospective studies on its usefulness with respect to the prognosis and utility of combined tumor markers are needed.

Keywords

Colorectal cancer CYFRA 21–1 CEA and CA 19–9 

Notes

Acknowledgments

The present research was conducted by the research fund of Dankook University in 2012.

Conflicts of Interest

None.

References

  1. 1.
    Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–50.PubMedCrossRefGoogle Scholar
  2. 2.
    Sarikaya I, Bloomston M, Povoski SP, Zhang J, Hall NC, Knopp MV, et al. FDG-PET scan in patients with clinically and/or radiologically suspicious colorectal cancer recurrence but normal CEA. World J Surg Oncol. 2007;5:64.PubMedCrossRefGoogle Scholar
  3. 3.
    Fiocchi F, Iotti V, Ligabue G, Malavasi N, Luppi G, Bagni B, et al. Role of carcinoembryonic antigen, magnetic resonance imaging, and positron emission tomography-computed tomography in the evaluation of patients with suspected local recurrence of colorectal cancer. Clin Imaging. 2011;35:266–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Lee JH, Park SG, Jee KN, Park DG, Namgung H, Song IH. Performance of FDG PET/CT in postoperative colorectal cancer patients with a suspected recurrence and a normal CEA level. Nucl Med Commun. 2010;31:576–82.PubMedGoogle Scholar
  5. 5.
    Riedl CC, Akhurst T, Larson S, Stanziale SF, Tuorto S, Bhargava A, et al. 18F-FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases. J Nucl Med. 2007;48:771–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Sanli Y, Kuyumcu S, Ozkan ZG, Kilic L, Balik E, Turkmen C, et al. The utility of FDG-PET/CT as an effective tool for detecting recurrent colorectal cancer regardless of serum CEA levels. Ann Nucl Med. 2012;56:551–8.CrossRefGoogle Scholar
  7. 7.
    Chang AC, Warren LR, Barreto SG, Williams R. Differing serum cea in primary and recurrent rectal cancer—a reflection of histology? World J Oncol. 2012;3:59–63.Google Scholar
  8. 8.
    Waisberg J, Contim-Neto L, Oliveira MSL, Matheus CO, Nagashima CA, Goffi FS. Determination of carcinoembryonic antigen levels in peripheral and draining venous blood in patients with colorectal carcinoma. Arq Gastroenterol. 2004;41:88–92.PubMedCrossRefGoogle Scholar
  9. 9.
    Booth S, King J, Leonard J, Dykes P. Serum carcinoembryonic antigen in clinical disorders. Gut. 1973;14:794–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Loewenstein M, Zamcheck N. Carcinoembryonic antigen (CEA) levels in benign gastrointestinal disease states. Cancer. 1978;42:1412–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Van der Schouw YT, Verbeek AL, Wobbes T, Segers MF, Thomas CM. Comparison of four serum tumour markers in the diagnosis of colorectal carcinoma. Br J Cancer. 1992;66:148–54.PubMedCrossRefGoogle Scholar
  12. 12.
    Chapman MH, Sandanayake NS, Andreola F, Dhar DK, Webster GJ, Dooley JS, et al. Circulating CYFRA 21–1 is a specific diagnostic and prognostic biomarker in biliary tract cancer. J Clin Exp Hepatol. 2011;1:6–12.PubMedCrossRefGoogle Scholar
  13. 13.
    Verwaal V, Zoetmulder F. Follow-up of patients treated by cytoreduction and chemotherapy for peritoneal carcinomatosis of colorectal origin. Eur J Surg Oncol. 2004;30:280–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Yang SH, Lin JK, Lai CR, Chen CC, Li A, Liang WY, et al. Risk factors for peritoneal dissemination of colorectal cancer. J Surg Oncol. 2004;87:167–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Zheng CX, Zhan WH, Zhao JZ, Zheng D, Wang DP, He YL, et al. The prognostic value of preoperative serum levels of CEA, CA19-9 and CA72-4 in patients with colorectal cancer. World J Gastroenterol. 2001;7:431–4.PubMedGoogle Scholar
  16. 16.
    Kantoush AA, Ahmed MM, Bushra SS. Evaluation of cyfra 21–1 as a diagnostic tool in lung cancer. J Appl Sci Res. 2009;5:1195–201.Google Scholar
  17. 17.
    Lumachi F, Marino F, Orlando R, Chiara GB, Basso SMM. Simultaneous multianalyte immunoassay measurement of five serum tumor markers in the detection of colorectal cancer. Anticancer Res. 2012;32:985–8.PubMedGoogle Scholar
  18. 18.
    Giovanella L, Ceriani L, Giardina G, Bardelli D, Tanzi F, Garancini S. Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA). Clin Chem Lab Med. 2002;40:298–303.PubMedGoogle Scholar
  19. 19.
    Brechot J, Chevret S, Nataf J, Le Gall C, Fretault J, Rochemaure J, et al. Diagnostic and prognostic value of cyfra 21–1 compared with other tumour markers in patients with non-small cell lung cancer: a prospective study of 116 patients. Eur J Cancer. 1997;33:385–91.PubMedGoogle Scholar
  20. 20.
    Molina R, Filella X, Auge J, Fuentes R, Bover I, Rifa J, et al. Tumor markers (CEA, CA 125, CYFRA 21–1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Tumor Biol. 2003;24:209–18.CrossRefGoogle Scholar
  21. 21.
    Molina R, Filella X, Augé JM, Bosch E, Torne A, Pahisa J, et al. CYFRA 21.1 in patients with cervical cancer: comparison with SCC and CEA. Anticancer Res. 2005;25:1765–71.PubMedGoogle Scholar
  22. 22.
    Jeong S, Park Y, Cho Y, Kim YR, Kim HS. Diagnostic values of urine CYFRA21-1, NMP22, UBC, and FDP for the detection of bladder cancer. Clin Chim Acta. 2012;414:93–100.PubMedCrossRefGoogle Scholar
  23. 23.
    Kulpa J, Wójcik E, Reinfuss M, Kołodziejski L. Carcinoembryonic antigen, squamous cell carcinoma antigen, CYFRA 21–1, and neuron-specific enolase in squamous cell lung cancer patients. Clin Chem. 2002;48:1931–7.PubMedGoogle Scholar
  24. 24.
    Maass J, Hoffmann-Fazel A, Goeroegh T, Hoffmann M, Meyer J, Gottschlich S, et al. Cyfra 21–1: a serological help for detection of distant metastases in head and neck cancer. Anticancer Res. 2000;20:2241–4.PubMedGoogle Scholar
  25. 25.
    Labianca R, Nordlinger B, Beretta G, Brouquet A, Cervantes A. Primary colon cancer: ESMO clinical practice guidelines for diagnosis, adjuvant treatment and follow-up. Ann Oncol. 2010;21:v70–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Scott NA, Wieand HS, Moertel CG, Cha SS, Beart RW, Lieber MM. Colorectal cancer: Dukes’ stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern. Arch Surg. 1987;122:1375–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Goldstein MJ, Mitchell EP. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Investig. 2005;23:338–51.CrossRefGoogle Scholar
  28. 28.
    Sheard MA, Vojtesek B, Simickova M, Valik D. Release of cytokeratin-18 and −19 fragments (TPS and CYFRA 21–1) into the extracellular space during apoptosis. J Cell Biochem. 2002;85:670–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Takada M, Masuda N, Matsuura E, Kusunoki Y, Matui K, Nakagawa K, et al. Measurement of cytokeratin 19 fragments as a marker of lung cancer by CYFRA 21–1 enzyme immunoassay. Br J Cancer. 1995;71:160–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Brockmann JG, Nottberg HS, Glodny B, Heinecke A, Senninger NJ. CYFRA 21–1 serum analysis in patients with esophageal cancer. Clin Cancer Res. 2000;6:4249–52.PubMedGoogle Scholar
  31. 31.
    Xu D, Li X, Zheng S, Jiang W. Quantitative real-time RT-PCR detection for CEA, CK20 and CK19 mRNA in peripheral blood of colorectal cancer patients. J Zhejiang Univ Sci B. 2006;7:445–51.PubMedCrossRefGoogle Scholar
  32. 32.
    Holdenrieder S, Stieber P, Liska V, Treska V, Topolcan O, Dreslerova J, et al. Cytokeratin serum biomarkers in patients with colorectal cancer. Anticancer Res. 2012;32:1971–6.PubMedGoogle Scholar
  33. 33.
    Wild N, Andres H, Rollinger W, Krause F, Dilba P, Tacke M, et al. A combination of serum markers for the early detection of colorectal cancer. Clin Cancer Res. 2010;16:6111–21.PubMedCrossRefGoogle Scholar
  34. 34.
    Uenishi T, Kubo S, Hirohashi K, Tanaka H, Shuto T, Yamamoto T, et al. Cytokeratin-19 fragments in serum (CYFRA 21–1) as a marker in primary liver cancer. Br J Cancer. 2003;88:1894–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Kim DW, Kim WH, Kim CG. Dual-time-point FDG PET/CT: is it useful for lymph node staging in patients with non-small-cell lung cancer? Nucl Med Mol Imaging. 2012;46:196–200.CrossRefGoogle Scholar
  36. 36.
    Jeong SY, Lee TH, Rhee CH, Cho AR, Kim BI, Cheon GJ, et al. 3′-Deoxy-3′-[18F]fluorothymidine and O-(2-[18F]fluoroethyl)-L-tyrosine PET in patients with suspicious recurrence of glioma after multimodal treatment: initial results of a retrospective comparative study. Nucl Med Mol Imaging. 2010;44:45–54.CrossRefGoogle Scholar

Copyright information

© Korean Society of Nuclear Medicine 2013

Authors and Affiliations

  1. 1.Department of Nuclear MedicineDankook University Medical CollegeCheonanRepublic of Korea

Personalised recommendations