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CD44 expression as a potential favorable marker for prognosis in mucoepidermoid carcinoma of salivary gland

  • Stella Marleen ,
  • Lisnawati Rachmadi ,
  • Diah Rini Handjari ,
  • Kusmardi Kusmardi ,


Background: Cluster of differentiation 44 (CD44) is one of the markers of cancer stem cells belonging to the cell adhesion molecule family, which may play a role in tumorigenesis of mucoepidermoid carcinoma (MEC) of the salivary gland. The histological grade is one of the most important factors for prognosis. This study was aimed to investigate the association between CD44 expressions with histological grade in MEC of the salivary gland.

Methods: In A cross-sectional study, 34 cases diagnosed with MEC in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia from 2012 to 2017 were included. Histological grade was classified into low-, moderate-, and high-grade. CD44 expression was done by immunohistochemistry staining and classified into weak and strong expressions.

Results: Eighteen cases (52.9%) were high-grade, 3 cases (8.8%) were moderate, and 13 cases (38.2%) were low-grade. Perineural invasion was found in 7 cases (20.6%) and mostly in high-grade tumors. CD44 expression was significantly associated with histological grade (p = 0.002, OR=0.09, 95%CI=0.02–0.48). Strong CD44 expression was found more in low-grade MEC.

Conclusions: This study suggests that strong CD44 expression may act as a potential favorable predictive factor for prognosis in the MEC of the salivary gland.


  1. Bell D, Holsinger CF, El-Naggar AK. CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible--diagnostic and histogenetic implications. Ann Diagn Pathol. 2010;14(6):396-401. doi:10.1016/j.anndiagpath.2010.05.009.
  2. McHugh CH, Roberts DB, El-Naggar AK, et al. Prognostic factors in mucoepidermoid carcinoma of the salivary glands. Cancer. 2012;118(16):3928-3936. doi:10.1002/cncr.26697.
  3. Seethala RR. An update on grading of salivary gland carcinomas. Head Neck Pathol. 2009;3(1):69-77. doi:10.1007/s12105-009-0102-9.
  4. Ali S, Sarhan M, Palmer FL, et al. Cause-specific mortality in patients with mucoepidermoid carcinoma of the major salivary glands. Ann Surg Oncol. 2013;20(7):2396-2404. doi:10.1245/s10434-013-2872-2.
  5. Adams A, Warner K, Pearson AT, et al. ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas. Oncotarget. 2015;6(29):26633-26650. doi:10.18632/oncotarget.5782.
  6. Nance MA, Seethala RR, Wang Y, et al. Treatment and survival outcomes based on histologic grading in patients with head and neck mucoepidermoid carcinoma. Cancer. 2008;113(8):2082-2089. doi:10.1002/cncr.23825.
  7. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105-111. doi:10.1038/35102167.
  8. Krause M, Dubrovska A, Linge A, Baumann M. Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev. 2017;109:63-73. doi:10.1016/j.addr.2016.02.002.
  9. Diehn M, Cho RW, Clarke MF. Therapeutic implications of the cancer stem cell hypothesis. Semin Radiat Oncol. 2009;19(2):78-86. doi:10.1016/j.semradonc.2008.11.002.
  10. Schwarz S, Rotter N. Human salivary gland stem cells: isolation, propagation, and characterization. Methods Mol Biol. 2012;879:403-442. doi:10.1007/978-1-61779-815-3_25,
  11. Yan Y, Zuo X, Wei D. Concise Review: Emerging Role of CD44 in Cancer Stem Cells: A Promising Biomarker and Therapeutic Target. Stem Cells Transl Med. 2015;4(9):1033-1043. doi:10.5966/sctm.2015-0048.
  12. Ayoub MSE-D, El-Shafei MM, Elias WY, El-kammar HA. Immunohistochemical evaluation of CD44 expression in mucoepidermoid carcinoma of human salivary glands. Future Dent J. 2018:1-8.
  13. Sillanpää S, Anttila MA, Voutilainen K, et al. CD44 expression indicates favorable prognosis in epithelial ovarian cancer. Clin Cancer Res. 2003;9(14):5318-5324.
  14. Horiguchi K, Toi M, Horiguchi S, et al. Predictive value of CD24 and CD44 for neoadjuvant chemotherapy response and prognosis in primary breast cancer patients. J Med Dent Sci. 2010;57(2):165-175.
  15. Tse GM, Tan PH, Ma TK, Gilks CB, Poon CS, Law BK. CD44s is useful in the differentiation of benign and malignant papillary lesions of the breast. J Clin Pathol. 200;58:1185-8. doi:10.1016/S1077-9108(08)70267-6
  16. Morath I, Hartmann TN, Orian-Rousseau V. CD44: More than a mere stem cell marker. Int J Biochem Cell Biol. 2016;81(Pt A):166-173. doi:10.1016/j.biocel.2016.09.009.
  17. Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. Arch Pathol Lab Med. 2018;142(11):1364-1382. doi:10.5858/arpa.2018-0902-SA.
  18. Binmadi N, Elsissi A, Elsissi N. Expression of cell adhesion molecule CD44 in mucoepidermoid carcinoma and its association with the tumor behavior. Head Face Med. 2016;12:8. Published 2016 Jan 29. doi:10.1186/s13005-016-0102-4.
  19. Qureshi SM, Janjua OS, Janjua SM. Mucoepidermoid carcinoma: a clinico-pathological review of 75 cases. J Oral Maxillofac Pathol. 2012;3:5-9.
  20. McFarlane S, Coulter JA, Tibbits P, et al. CD44 increases the efficiency of distant metastasis of breast cancer. Oncotarget. 2015;6(13):11465-11476. doi:10.18632/oncotarget.3410.
  21. Lestari AAW, Prabawa IPY, Wiranata S, Supadmanaba IGP. High eosinophilic lymphocyte ratio (ELR) related with subtype of breast cancer in Sanglah General Hospital. Annals of Oncology. 2018;29(suppl_9). DOI:
  22. Joshua B, Kaplan MJ, Doweck I, et al. Frequency of cells expressing CD44, a head and neck cancer stem cell marker: correlation with tumor aggressiveness. Head Neck. 2012;34(1):42-49. doi:10.1002/hed.21699.
  23. Karjalainen JM, Tammi RH, Tammi MI, et al. Reduced level of CD44 and hyaluronan associated with unfavorable prognosis in clinical stage I cutaneous melanoma. Am J Pathol. 2000;157(3):957-965. doi:10.1016/S0002-9440(10)64608-1.
  24. Nanashima A, Yamaguchi H, Sawai T, et al. Prognostic factors in hepatic metastases of colorectal carcinoma: immunohistochemical analysis of tumor biological factors. Dig Dis Sci. 2001;46(8):1623-1628. doi:10.1023/a:1010680815954.
  25. Vis AN, Noordzij MA, Fitoz K, Wildhagen MF, Schröder FH, van der Kwast TH. Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer. J Urol. 2000;164(6):2156-2161.
  26. Louderbough JM, Schroeder JA. Understanding the dual nature of CD44 in breast cancer progression. Mol Cancer Res. 2011;9(12):1573-1586. doi:10.1158/1541-7786.MCR-11-0156.
  27. Yang C, Cao M, Liu H, et al. The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering. J Biol Chem. 2012;287(51):43094-43107. doi:10.1074/jbc.M112.349209.
  28. Chanmee T, Ontong P, Kimata K, Itano N. Key Roles of Hyaluronan and Its CD44 Receptor in the Stemness and Survival of Cancer Stem Cells. Front Oncol. 2015;5:180. Published 2015 Aug 10. doi:10.3389/fonc.2015.00180.

How to Cite

Marleen, S., Rachmadi, L., Handjari, D. R., & Kusmardi, K. (2022). CD44 expression as a potential favorable marker for prognosis in mucoepidermoid carcinoma of salivary gland. Bali Medical Journal, 11(1), 106–111.




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Stella Marleen
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Lisnawati Rachmadi
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Diah Rini Handjari
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Kusmardi Kusmardi
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