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

Document Type : Research/Original Article


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

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



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.


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.
2. NCIN (2010) National Cancer
Intelligence Network - Routes to
Diagnosis, Data Briefing. 2010
[Available from:
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.
4. Imperiale TF, Ransohoff DF, Itzkowitz
SH. Multitarget stool DNA testing
for colorectal-cancer screening. The
New England journal of medicine.
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.
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).
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.
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.
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.
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.
15. Gold P, Freedman SO.
The Journal of experimental medicine.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.