Tumor Biology

, Volume 36, Issue 4, pp 2793–2799 | Cite as

Clinical implication of CD166 expression in salivary gland tumor

  • Azadeh Andisheh-Tadbir
  • Mohammad Javad Ashraf
  • Bijan Khademi
  • Shahab Ahmadi
Research Article


CD166 is a glycoprotein of immunoglobulin superfamily of adhesion molecules which is overexpressed in many tumors. However, no published literature was found concerning CD166 expression in salivary gland tumor. The purpose of this study was to examine the CD166 expression in the salivary gland tumor by an immunohistochemical approach, to examine the clinical implication of this marker in the prognosis and diagnosis of the salivary gland tumor. In this study, 45 samples of salivary tumors from Khalili Hospital archive including 15 cases of pleomorphic adenoma, 16 cases of mucoepidermoid carcinoma, 14 cases of adenoid cystic carcinoma, and 15 normal salivary glands were selected for immunohistochemistry (IHC) method staining for CD166. CD166 immunoreactivity in malignant tumors (adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC)) (56.7 ± 14.05) was significantly higher than that of pleomorphic adenoma (PA) (34.3 ± 17.07) (P < 0.000) and higher in the PA than normal salivary gland (13.2 ± 12.1) (P = 0.001). CD166 expression was significantly higher in the high-grade tumors (90.3 ± 11.07) compared to low-grade (65.11 ± 27.08) malignant tumors (P = 0.002). CD166 expression showed a significant association with tumor size and the clinical stage (P < 0.001). In conclusion, an overexpression of CD166 was detected in the benign and malignant salivary gland tumors and its expression in the malignant tumor was associated with the aggressive behavior and tumor progression. For this reason, CD166 may be one of the potential biomarkers for predicting tumor behavior in the prognosis of this disease.


Salivary gland tumor Pleomorphic adenoma Adenoid cystic carcinoma Mucoepidermoid carcinoma CD166 



The authors thank the Vice-Chancellery of Shiraz University of Medical Sciences for supporting this research (Grant #92-01-03-6495). This manuscript is based on the thesis of Shahab Ahmadi for partial fulfillment of DDS degree. The authors are grateful to Dr. Sh. Hamedani (DDS, MSC) for his suggestions and editorial assistance, and also, thanks to Dr. M. Vossoughi of the Dental Research Development Center of the Dental School, for the statistical analysis.


  1. 1.
    Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986;8(3):177–84.CrossRefPubMedGoogle Scholar
  2. 2.
    Alves FA, Pires FR, De Almeida OP, Lopes MA, Kowalski LP. PCNA, Ki-67 and p53 expressions in submandibular salivary gland tumours. Int J Oral Maxillofac Surg. 2004;33(6):593–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Jones AV, Franklin CD. An analysis of oral and maxillofacial pathology found in adults over a 30-year period. J Oral Pathol Med. 2006;35(7):392–401.CrossRefPubMedGoogle Scholar
  4. 4.
    Speight PM, Barrett AW. Salivary gland tumours. Oral Dis. 2002;8(5):229–40.CrossRefPubMedGoogle Scholar
  5. 5.
    Ito FA, Ito K, Vargas PA, de Almeida OP, Lopes MA. Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. Int J Oral Maxillofac Surg. 2005;34(5):533–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Ota T, Ota K, Jono H, Fujimori H, Ueda M, Shinriki S, et al. Midkine expression in malignant salivary gland tumors and its role in tumor angiogenesis. Oral Oncol. 2010;46(9):657–61.CrossRefPubMedGoogle Scholar
  7. 7.
    Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19(3):294–308.CrossRefPubMedGoogle Scholar
  8. 8.
    Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 2007;7(6):415–28.CrossRefPubMedGoogle Scholar
  9. 9.
    Nair KS, Naidoo R, Chetty R. Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value. J Clin Pathol. 2005;58(4):343–51.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Tuyns AJ, Estève J, Raymond L, Berrino F, Benhamou E, Blanchet F, et al. Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC international case–control study in Turin and Varese (Italy), Zaragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int J Cancer. 1988;41(4):483–91.CrossRefPubMedGoogle Scholar
  11. 11.
    Weidle UH, Eggle D, Klostermann S, Swart GW. ALCAM/CD166: cancer-related issues. Cancer Genomics Proteomics. 2010;7(5):231–43.PubMedGoogle Scholar
  12. 12.
    van Kilsdonk JW, Wilting RH, Bergers M, van Muijen GN, Schalkwijk J, van Kempen LC, et al. Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule. Cancer Res. 2008;68(10):3671–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Ofori-Acquah SF, King JA. Activated leukocyte cell adhesion molecule: a new paradox in cancer. Transl Res. 2008;151(3):122–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A. 2007;104(24):10158–63.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Campbell IG, Foulkes WD, Senger G, Trowsdale J, Garin-Chesa P, Rettig WJ. Molecular cloning of the B-CAM cell surface glycoprotein of epithelial cancers: a novel member of the immunoglobulin superfamily. Cancer Res. 1994;54(22):5761–5.PubMedGoogle Scholar
  16. 16.
    Economopoulou P, Hanby A, Odell EW. Expression of E-cadherin, cellular differentiation and polarity in epithelial salivary neoplasms. Oral Oncol. 2000;36(6):515–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Franchi A, Gallo O, Bocciolini C, Franchi L, Paglierani M, Santucci M. Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity. Am J Clin Pathol. 1999;111(1):43–50.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang ZY, Wu YQ, Zhang WG, Tian Z, Cao J. The expression of E-cadherin-catenin complex in adenoid cystic carcinoma of salivary glands. Chin J Dent Res. 2000;3(3):36–9.PubMedGoogle Scholar
  19. 19.
    Mezzanzanica D, Fabbi M, Bagnoli M, Staurengo S, Losa M, Balladore E, et al. Subcellular localization of activated leukocyte cell adhesion molecule is a molecular predictor of survival in ovarian carcinoma patients. Clin Cancer Res. 2008;14(6):1726–33.CrossRefPubMedGoogle Scholar
  20. 20.
    Burkhardt M, Mayordomo E, Winzer KJ, Fritzsche F, Gansukh T, Pahl S, et al. Cytoplasmic overexpression of ALCAM is prognostic of disease progression in breast cancer. J Clin Pathol. 2006;59(4):403–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kristiansen G, Pilarsky C, Wissmann C, Stephan C, Weissbach L, Loy V, et al. ALCAM/CD166 is up-regulated in low-grade prostate cancer and progressively lost in high-grade lesions. Prostate. 2003;54(1):34–43.CrossRefPubMedGoogle Scholar
  22. 22.
    Rosso O, Piazza T, Bongarzone I, Rossello A, Mezzanzanica D, Canevari S, et al. The ALCAM shedding by the metalloprotease ADAM17/TACE is involved in motility of ovarian carcinoma cells. Mol Cancer Res. 2007;5(12):1246–53.CrossRefPubMedGoogle Scholar
  23. 23.
    Jezierska A, Matysiak W, Motyl T. ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy. Med Sci Monit. 2006;12(8):BR263–73.PubMedGoogle Scholar
  24. 24.
    Weichert W, Knösel T, Bellach J, Dietel M, Kristiansen G. ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival. J Clin Pathol. 2004;57(11):1160–4.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kristiansen G, Pilarsky C, Wissmann C, Kaiser S, Bruemmendorf T, Roepcke S, et al. Expression profiling of microdissected matched prostate cancer samples reveals CD166/MEMD and CD24 as new prognostic markers for patient survival. J Pathol. 2005;205(3):359–76.CrossRefPubMedGoogle Scholar
  26. 26.
    Jezierska A, Olszewski WP, Pietruszkiewicz J, Olszewski W, Matysiak W, Motyl T. Activated leukocyte cell adhesion molecule (ALCAM) is associated with suppression of breast cancer cells invasion. Med Sci Monit. 2006;12(7):BR245–56.PubMedGoogle Scholar
  27. 27.
    Hong X, Michalski CW, Kong B, Zhang W, Raggi MC, Sauliunaite D, et al. ALCAM is associated with chemoresistance and tumor cell adhesion in pancreatic cancer. J Surg Oncol. 2010;101(7):564–9.CrossRefPubMedGoogle Scholar
  28. 28.
    van den Brand M, Takes RP, Blokpoel-deRuyter M, Slootweg PJ, van Kempen LC. Activated leukocyte cell adhesion molecule expression predicts lymph node metastasis in oral squamous cell carcinoma. Oral Oncol. 2010;46(5):393–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Zhi YH, Song MM, Wang PL, Zhang T, Yin ZY. Suppression of matrix metalloproteinase-2 via RNA interference inhibits pancreatic carcinoma cell invasiveness and adhesion. World J Gastroenterol. 2009;15(9):1072–8.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lunter PC, van Kilsdonk JW, van Beek H, Cornelissen IM, Bergers M, Willems PH, et al. Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a novel actor in invasive growth, controls matrix metalloproteinase activity. Cancer Res. 2005;65(19):8801–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Sawhney M, Matta A, Macha MA, Kaur J, DattaGupta S, Shukla NK, et al. Cytoplasmic accumulation of activated leukocyte cell adhesion molecule is a predictor of disease progression and reduced survival in oral cancer patients. Int J Cancer. 2009;124(9):2098–105.CrossRefPubMedGoogle Scholar
  32. 32.
    Ihnen M, Kress K, Kersten JF, Kilic E, Choschzick M, Zander H, et al. Relevance of activated leukocyte cell adhesion molecule (ALCAM) in tumor tissue and sera of cervical cancer patients. BMC Cancer. 2012;12:140.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Yamada K. Comparative expression of E-cadherin, α and β-catenin in salivary gland tumors. In: Namba M, editor.: Acta Histochem Cytochem; 1999. p. 305–10.Google Scholar
  34. 34.
    Tadbir AA, Pardis S, Ashkavandi ZJ, Najvani AD, Ashraf MJ, Taheri A, et al. Expression of Ki67 and CD105 as proliferation and angiogenesis markers in salivary gland tumors. Asian Pac J Cancer Prev. 2012;13(10):5155–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Ni J, Cozzi P, Hao J, Beretov J, Chang L, Duan W, et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 2013;45(12):2736–48.CrossRefPubMedGoogle Scholar
  36. 36.
    Wang NS, Wei M, Ma WL, Meng W, Zheng WL. Knockdown of CD44 enhances chemosensitivity of acute myeloid leukemia cells to ADM and Ara-C. Tumour Biol. 2013.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Azadeh Andisheh-Tadbir
    • 1
  • Mohammad Javad Ashraf
    • 2
  • Bijan Khademi
    • 3
  • Shahab Ahmadi
    • 4
  1. 1.Department of Oral and Maxillofacial Pathology, School of DentistryShiraz University of Medical SciencesShirazIran
  2. 2.Department of Pathology, School of MedicineShiraz University of Medical SciencesShirazIran
  3. 3.Department of Otolaryngology, Khalili Hospital, Shiraz Institute for Cancer ResearchShiraz University of Medical SciencesShirazIran
  4. 4.School of DentistryShiraz University of Medical SciencesShirazIran

Personalised recommendations