Cytokeratin Fragment 21.1 (CYFRA 21.1) is a Useful Tumor Marker in Colonic Adenocarcinoma: A Cross-sectional Study

Document Type : Research/Original Article

Authors

1 Department of General Surgery, Government Medical College, Trivandrum, Kerala, India.

2 Department of General Surgery, Government Medical College, Konni, Kerala, India.

Abstract

Background: Colorectal carcinoma forms a major cause of cancer-related mortality and morbidity, while having increasing incidence, all over the world. Carcino Embryonic Antigen(CEA) is the established tumour marker for colorectal cancer, with uses in screening, pre treatment staging, post therapeutic monitoring and detecting recurrence. However, CEA is affected by multiple factors including smoking or benign gastrointestinal diseases. Hence the need for investigating alternative tumour markers like Cytokeratin fragment 21-1(CYFRA 21-1).
Materials and Methods: The objective of this Cross Sectional study were to find if the combination of CYFRA 21-1 and CEA is superior to CEA alone as a diagnostic marker in colonic cancer. From June 2016 to December 2019, 69 consecutive patients with a histologically confirmed diagnosis of colonic adenocarcinoma were included in the study. The serum levels of both tumour markers were analysed before starting any definite treatment. Sensitivity and Positive Predictive Values for both tumour markers were calculated. Correlation between tumour markers was tested using Pearson’s correlation. Correlation between TNM stage and tumour marker was tested using Spearman’s Rho test.
Results: 41 patients had elevated CEA while 33 patients had elevated CYFRA 21-1. CEA and CYFRA 21-1 mildly positively correlated with each other, with an R value of 0.2598(p value 0.031). Spearman’s correlation with clinical stage of cancer was found to be 0.50834 for CEA(p value < 0.005) and 0.59828 for CYFRA 21-1(p value < 0.005). Sensitivity of CEA 59.42%, while that of CYFRA 21-1 was 47.83%. The combination of both had a sensitivity of 75%.
Conclusion:. The combination of CYFRA 21-1 and CEA was found to be more effective in picking up cases of colonic cancer than CEA alone. Both CYFRA 21-1 and CEA correlated well with the stage of disease. A combination of these biomarkers has great potential to evolve as diagnostic aid in colonic cancer.

Keywords

References

  1. 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 journal of surgical oncology. 2007;5:64.
  2. NCIN (2010) National Cancer Intelligence Network - Routes to Diagnosis, Data Briefing. 2010 [Available from: http://www.ncin.org. uk/publications/data_briefings/ routes to diagnosis.aspx. c.201.
  3. Lindholm E, Brevinge H, Haglind E. Survival benefit in a randomized clinical trial of faecal occult blood
    screening for colorectal cancer. The British journal of surgery. 2008;95(8):1029-36.
  4. Imperiale TF, Ransohoff DF, Itzkowitz SH. Multitarget stool DNA testing for colorectal-cancer screening. The
    New England journal of medicine. 2014;371(2):187-8.
  5. Logan RF, Patnick J, Nickerson C, Coleman L, Rutter MD, von Wagner C. Outcomes of the Bowel Cancer
    Screening Programme (BCSP) in England after the first 1 million tests. Gut. 2012;61(10):1439-46.
  6. Whitlock EP, Lin J, Liles E, Beil T, Fu R, O’Connor E, et al. U.S. Preventive Services Task Force Evidence
    Syntheses, formerly Systematic Evidence Reviews. Screening for Colorectal Cancer: An Updated
    Systematic Review. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008.
  7. Holme Ø, Bretthauer M, Fretheim A, Odgaard-Jensen J, Hoff G. Flexible sigmoidoscopy versus faecal
    occult blood testing for colorectal cancer screening in asymptomatic individuals. The Cochrane
    database of systematic reviews. 2013;2013(9):Cd009259.
  8. Atkin WS, Edwards R, Kralj- Hans I, Wooldrage K, Hart AR, Northover JM, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial.                                       Lancet (London, England). 2010;375(9726):1624-33.
  9. Cairns SR, Scholefield JH, Steele RJ, Dunlop MG, Thomas HJ, Evans GD, et al. Guidelines for colorectal
    cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59(5):666-89.
  10. Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, et al. Screening and surveillance for the
    early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American
    Cancer Society, the US Multi- Society Task Force on Colorectal Cancer, and the American College
    of Radiology. Gastroenterology. 2008;134(5):1570-95.
  11. Robb K, Power E, Kralj-Hans I, Edwards R, Vance M, Atkin W, et al. Flexible sigmoidoscopy screening for colorectal cancer: uptake in a population-based pilot programme. Journal of medical screening. 2010;17(2):75-8.
  12. Taylor DP, Cannon-Albright LA, Sweeney C, Williams MS, Haug PJ, Mitchell JA, et al. Comparison of compliance for colorectal cancer screening and surveillance by colonoscopy based on risk. Genetics in medicine : official journal of
    the American College of Medical Genetics. 2011;13(8):737-43.
  13. Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L, et al. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.
    International journal of cancer. 2014;134(11):2513-22.
  14. Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. Journal of clinical oncology : official journal of the American
    Society of Clinical Oncology. 2006;24(33):5313-27.
  15. Gold P, Freedman SO. DEMONSTRATION OF TUMORSPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY
    IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES.                                                                             The Journal of experimental medicine. 1965;121(3):439-62.
  16. 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. Clinical imaging. 2011;35(4):266-73.
  17. Chang AC, Warren LR, Barreto SG, Williams R. Differing Serum Cea in Primary and Recurrent Rectal Cancer
    - A Reflection of Histology? World journal of oncology. 2012;3(2):59-63.
  18. van der Schouw YT, Verbeek AL, Wobbes T, Segers MF, Thomas CM. Comparison of four serum tumour
    markers in the diagnosis of colorectal carcinoma. British journal of cancer. 1992;66(1):148-54.
  19. Lumachi F, Marino F, Orlando R, Chiara GB, Basso SM. Simultaneous mult ianalyte immunoassay measurement of five serum tumor markers in the detection of colorectal cancer. Anticancer research. 2012;32(3):985-8.
  20. 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). Clinical chemistry and laboratory medicine. 2002;40(3):298-303.
  21. Kantoush AA AM, Bushra SS. Evaluation of CYFRA 21–1 as a diagnostic tool in lung cancer.                                          J Appl Sci Res 2009;5:1195–201.
  22. Lee JH. Clinical Usefulness of Serum CYFRA 21-1 in Patients with Colorectal Cancer. Nuclear medicine and molecular imaging. 2013;47(3):181-7.
  23. Goldstein MJ, Mitchell EP. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer investigation. 2005;23(4):338-51.
  24. Thomas DS, Fourkala EO, Apostolidou S, Gunu R, Ryan A, Jacobs I, et al. Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples.                                    British journal of cancer. 2015;113(2):268-74.
  25. Hammar st röm S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Seminars in cancer biology. 1999;9(2):67-81.
  26. Wanebo JH, Stearns M, Schwartz MK. Use of CEA as an indicator of early recurrence and as a guide to a selected second-look procedure in patients with colorectal cancer. Annals of surgery. 1978;188(4):481-93.
  27. Goslin R, O’Brien MJ, Steele G, Mayer R, Wilson R, Corson JM, et al. Correlation of Plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer. The American journal of medicine. 1981;71(2):246-53.
  28. Palmqvist R, Engarås B, Lindmark G, Hallmans G, Tavelin B, Nilsson O, et al. Prediagnostic levels of carcinoembryonic antigen and CA 242 in colorectal cancer: a matched casecontrol study. Diseases of the colon
    and rectum. 2003;46(11):1538-44.
  29. Ladd JJ, Busald T, Johnson MM, Zhang Q, Pitteri SJ, Wang H, et al. Increased plasma levels of the APCinteracting
    protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women. Cancer
    prevention research (Philadelphia, Pa). 2012;5(4):655-64.
  30. Guittet L, Bouvier V, Mariotte N, Vallee JP, Arsène D, Boutreux S, et al. Comparison of a guaiac based and an
    immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population.
    Gut. 2007;56(2):210-4.
  31. Church TR, Wandell M, Lofton- Day C, Mongin SJ, Burger M, Payne SR, et al. Prospective evaluation of
    methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63(2):317-25.
  32. Lee JK, Liles EG, Bent S, Levin TR, Corley DA. Accuracy of fecal immunochemical tests for colorectal
    cancer: systematic review and metaanalysis. Annals of internal medicine. 2014;160(3):171.
  33. Raginel T, Puvinel J, Ferrand O, Bouvier V, Levillain R, Ruiz A, et al. A population-based comparison of
    immunochemical fecal occult blood tests for colorectal cancer screening. Gastroenterology. 2013;144(5):918-25.
  34. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA. Hepatic toxicity associated with fluorouracil
    plus levamisole adjuvant therapy. Journal of clinical oncology : official journal of the American
    Society of Clinical Oncology. 1993;11(12):2386-90.
  35. Gawel SH, Lucht M, Gomer H, Treado P, Christensen IJ, Nielsen HJ, et al. Evaluation of algorithm development
    approaches: Development of biomarker panels for early detection of colorectal lesions. Clinica chimica
    acta; international journal of clinical chemistry. 2019;498:108-15.
  36. Lim DH, Lee JH, Kim JW. Feasibility of CYFRA 21-1 as a serum biomarker for the detection of colorectal
    adenoma and advanced colorectal adenoma in people over the age of 45.                                                         Journal of clinical laboratory analysis. 2018;32(1).
  37. Xu D, Li XF, Zheng S, Jiang WZ. Quantitative real-time RT-PCR detection for CEA, CK20 and CK19 mRNA in peripheral blood of colorectal cancer patients. Journal of Zhejiang University Science B. 2006;7(6):445-51.
  38. Holdenrieder S, Stieber P, Liska V, Treska V, Topolcan O, Dreslerova J, et al. Cytokeratin serum biomarkers
    in patients with colorectal cancer. Anticancer research. 2012;32(5):1971-6.
  39. Dressen K, Hermann N, Manekeller S, Walgenbach-Bruenagel G, Schildberg FA, Hettwer K, et al. Diagnostic Performance of a Novel Multiplex Immunoassay in Colorectal Cancer. Anticancer research. 2017;37(5):2477-86.
Iranian Journal of Colorectal Research
Volume 10, Issue 4
December 2022
Pages 143-149

Files

Share

How to cite

Statistics