Serum Levels of Cyfra 21 in Patients with Benign and Malignant Salivary Gland Tumors

Document Type : Original


1 Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Otolaryngology Research Center, Department of Otolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Institute of Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.


Cyfra 21 is a serum-soluble fragment of cytokeratin19. Increased Cyfra 21 serum levels and their benefit as a tumor marker have been shown in some malignancies. This study aimed to evaluate the serum levels of Cyfra 21 in patients with benign and malignant salivary gland tumors.
Materials and Methods:
In this cross-sectional study, the serum level of Cyfra 21 in 44 patients with malignant salivary gland tumors and 16 cases of pleomorphic adenoma were compared with 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Data were analyzed statistically using the Kruskal Wallis test, analysis of variance (ANOVA) and Spearman’s correlation tests.
Mean serum levels of Cyfra 21 were 0.135 ± 0.285 ng/ ml in the control group, 0.167 ± 0.142 ng/ ml in patients with pleomorphic adenoma and 1.059 ± 3.251 ng/ml in patients with malignant salivary gland tumors. There was no significant difference among groups. Cyfra 21 levels did not correlate with location of tumor, clinical stage or cigarette smoking.
Results of the present study showed no significant difference in Cyfra 21 serum level in salivary gland tumors compared with normal individuals. In addition, Cyfra 21 serum level was not sufficiently sensitive to function as a tumor marker in salivary gland tumors.


Main Subjects

1. Jaafari-Ashkavandi Z, Ashraf MJ, Moshaverinia M. Salivary gland tumors: a clinicopathologic study of 366 cases in southern Iran. Asian Pac J Cancer Prev 2013;14(1):27-30.
2. Mendenhall WM, Amdur RJ, Palta JR. Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls. J Clin Oncol 2006; 24(17):2618–23.
3. Bigbee W, Herberman RB. Tumor Markers and Immunodiagnosis. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003;6:209-20.
4. Haug U, Rothenbacher D, Wente M, Seiler C, Stegmaier C, Brenner H. Tumour M2-PK as a stool marker for colorectal cancer: comparative analysis in a large sample of unselected older adults vs colorectal cancer patients. Br J Cancer 2007; 96(9): 1329–34.
5. Jaafari-Ashkavandi Z, Moshref M, Mashhadi-Abbas F, Sargolzaie S, Taghavi N. Evaluation of CD31 Expression and Mast Cell Count in Dysplastic Lesions and Squamous Cell Carcinoma of the Oral Cavity. Iran Red Crescent Med J 2010; 12(3):272–6.
6. Bustin S, Gyselman V, Williams N, Dorudi S. Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients. Br J Cancer 1999;79(11-12):1813.
7. Fukunaga Y, Bandoh S, Fujita J, Yang Y, Ueda Y, Hojo S, et al. Expression of cytokeratin 8 in lung cancer cell lines and measurement of serum cytokeratin 8 in lung cancer patients. Lung cancer (Amsterdam, Netherlands) 2002;38(1):31–8.
8. Rastel D, Ramaioli A, Cornillie F, Thirion B. CYFRA 21-1, a sensitive and specific new tumour marker for squamous cell lung cancer. Report of the first European multicentre evaluation. CYFRA 21-1 Multicentre Study Group. Eur J Cancer 1994; 30(5):601–6.
9. Pujol JL, Molinier O, Ebert W, Daures J, Barlesi F, Buccheri G, et al. CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients. Br J Cancer 2004; 90(11):2097–105.
10. Doweck I, Barak M, Uri N, Greenberg E. The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease. Br J Cancer 2000; 83(12):1696.
11. Rajkumar K, Ramya R, Nandhini G, Rajashree P, Ramesh Kumar A, Nirmala Anandan S. Salivary and serum level of CYFRA 21‐1 in oral precancer and oral squamous cell carcinoma. Oral Dis 2015; 21(1):90–6.
12. Kawaguchi H, Ohno S, Miyazaki M, Hashimoto K, Egashira A, Saeki H, et al. CYFRA 21‐1 determination in patients with esophageal squamous cell carcinoma. Cancer 2000; 89(7): 1413–7.
13. Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, et al. The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathol 2006; 49(2): 138–51.
14. Cao X, Zhang L, Feng GR, Yang J, Wang RY, Li J, et al. Preoperative Cyfra21-1 and SCC-Ag serum titers predict survival in patients with stage II esophageal squamous cell carcinoma. J Trans Med 2012;10(1):1.
15. Loyola AM, De Sousa S, Araújo NSd, Araújo VCd. Study of minor salivary gland mucoepidermoid carcinoma differentiation based on immunohistochemical expression of cytokeratins, vimentin and muscle-specific actin. Oral Oncol 1998; 34(2):112–8.
16. Altemani A, Martins M, Freitas L, Soares F, Araújo N, Araújo V. Carcinoma ex pleomorphic adenoma (CXPA): immunoprofile of the cells involved in carcinomatous progression. Histopathol 2005; 46(6):635–41.
17. Azevedo RS, de Almeida OP, Kowalski LP, Pires FR. Comparative cytokeratin expression in the different cell types of salivary gland mucoepidermoid carcinoma. Head Neck Pathol 2008; 2(4):257–64.
18. Li X, Shi Z, Wang Y, Liu Y, Liu T. Immunohistochemical expression of cytokeratins in human salivary gland acinic cell carcinomas. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 120 (2):248–57.
19. Jose J, Sunil P, Madhavan Nirmal R, Varghese SS. CYFRA 21-1: AN OVERVIEW. Oral Maxillofac Pathol J 2013;4(2).
20. Kosacka M, Jankowska R. Comparison of cytokeratin 19 expression in tumor tissue and serum CYFRA 21-1 levels in non-small cell lung cancer. Polskie Archiwum Medycyny Wewnetrznej 2009;119(1–2):33–7.
21. Okamura K, Takayama K, Izumi M, Harada T, Furuyama K, Nakanishi Y. Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer. Lung cancer (Amsterdam, Netherlands) 2013;80(1):45–9.
22. Nakata B, Takashima T, Ogawa Y, Ishikawa T, Hirakawa K. Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer. Br J Cancer 2004;91(5):873–8.
23. Doweck I, Barak M, Greenberg E, Uri N, Kellner J, Lurie M, et al. Cyfra 21-1: A new potential tumor marker for squamous cell carcinoma of head and neck Arch Otolaryngol Head Neck Surg 1995;121(2):177–81.
24. Ho S, Leung W, Yuen J, Johnson P. Serum levels of CYFRA 21-1 in nasopharyngeal carcinoma and its possible role in monitoring of therapy. Eur J Cancer (B): Oral Oncol 1996; 32(6): 377–80.
25. Wieskopf B, Demangeat C, Purohit A, Stenger R, Gries P, Kreisman H, et al. Cyfra 21-1 as a biologic marker of non-small cell lung cancer. Evaluation of sensitivity, specificity, and
prognostic role. Chest 1995;108(1):163–9.
26. Wu HH, Wang PH, Yeh JY, Chen YJ, Yen MS, Huang RL, et al. Serum cytokeratin-19 fragment (Cyfra 21-1) is a prognostic indicator for epithelial ovarian cancer. Taiwan J Obstet Gynecol 2014; 53(1): 30–4.
27. Tsai SC, Kao C, Wang S. Study of a new tumor marker, CYFRA 21-1, in squamous cell carcinoma of the cervix, and comparison with squamous cell carcinoma antigen. Neoplasma 1996;43(1):27–9.
28. Jaafari- Ashkavandi Z, Ashraf M. A clinico-pathologic study of 142 orofacial tmors in children and adolescents in southern iran. Iran J Pediatr 2011;21(3):367-72.