Head and Neck Pathology

, Volume 6, Issue 1, pp 38–47 | Cite as

Lack of Association of Cadherin Expression and Histopathologic Type, Metastasis, or Patient Outcome in Oropharyngeal Squamous Cell Carcinoma: A Tissue Microarray Study

  • O. C. Ukpo
  • W. L. Thorstad
  • Q. Zhang
  • J. S. LewisJr.
Original Paper


Altered cadherin expression is important for metastasis in many carcinomas including head and neck squamous cell carcinoma (SCC). We evaluated E- and N-cadherin expression specifically in oropharyngeal SCC and correlated this with clinical and pathologic features. Oropharyngeal SCC patients with clinical follow up information were identified from clinician databases from 1996 through 2007 and tissue microarrays created. Tumors had been previously typed histopathologically as keratinizing, non-keratinizing, or non-keratinizing with maturation, and had known p16 and human papillomavirus status, respectively. Immunohistochemistry was performed on the microarrays, and staining was evaluated for presence and intensity (0 = negative, 1 = weak, 2 = moderate, 3 = strong) both visually and also with digital image analysis software. Of 154 cases, E-cadherin was expressed in 152 (98.7%) and N-cadherin in 17 (11.5%). Neither E- nor N-cadherin expression was statistically significantly associated with histopathologic type (P = 0.082 and P = 0.228, respectively). E-cadherin staining intensity was not statistically significantly associated with nodal or distant metastasis, either visually or by image analysis, (P = 0.098 and P = 0.963 respectively) nor was N-cadherin (P = 0.228 and P = 0.935 respectively). Neither E- nor N-cadherin expression was associated with death from disease (P = 0.995; P = 0.964, respectively). E-cadherin is extensively expressed by oropharyngeal SCC, even the non-keratinizing type. Our results suggest that cadherin expression may not be a predictor for nodal or distant metastasis in these tumors. Mechanisms independent of cadherin expression may be important for metastases in oropharyngeal SCC.


Oropharyngeal Squamous cell carcinoma E-cadherin N-cadherin Survival Immunohistochemistry p16 Human papillomavirus 


  1. 1.
    Ukpo OC, Pritchett CV, Lewis JE, et al. Human papillomavirus-associated oropharyngeal squamous cell carcinomas: primary tumor burden and survival in surgical patients. Ann Otol Rhinol Laryngol. 2009;118(5):368–73.PubMedGoogle Scholar
  2. 2.
    Ritchie JM, Smith EM, Summersgill KF, et al. Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer. 2003;104(3):336–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(16):1576.CrossRefGoogle Scholar
  4. 4.
    El-Mofty SK, Patil S. Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(3):339–45.PubMedCrossRefGoogle Scholar
  5. 5.
    El-Mofty SK, Lu DW. Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the palatine tonsil, and not the oral cavity, in young patients: a distinct clinicopathologic and molecular disease entity. Am J Surg Pathol. 2003;27(11):1463–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Chernock RD, El-Mofty SK, Thorstad WL, et al. HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome. Head Neck Pathol. 2009;3(3):186–94.PubMedCrossRefGoogle Scholar
  7. 7.
    Adelstein DJ, Ridge JA, Gillison ML, et al. Head and neck squamous cell cancer and the human papillomavirus: summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, D.C. Head Neck 2009;31(11):1393–422.Google Scholar
  8. 8.
    Mattijssen V, Peters HM, Schalkwijk L, et al. E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. Int J Cancer. 1993;55(4):580–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Duband JL, Dufour S, Hatta K, et al. Adhesion molecules during somitogenesis in the avian embryo. J Cell Biol. 1987;104(5):1361–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Karayiannakis AJ, Syrigos KN, Chatzigianni E, et al. E-cadherin expression as a differentiation marker in gastric cancer. Hepatogastroenterology. 1998;45(24):2437–42.PubMedGoogle Scholar
  11. 11.
    Syrigos KN, Krausz T, Waxman J, et al. E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded tissues: correlation with histopathological grade, tumour stage and survival. Int J Cancer. 1995;64(6):367–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Karayiannakis AJ, Syrigos KN, Chatzigianni E, et al. Aberrant E-cadherin expression associated with loss of differentiation and advanced stage in human pancreatic cancer. Anticancer Res. 1998;18(6A):4177–80.PubMedGoogle Scholar
  13. 13.
    Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998;153(2):333–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Shnayder Y, Kuriakose MA, Yee H, et al. Adhesion molecules as prognostic factors in nasopharyngeal carcinoma. Laryngoscope. 2001;111(10):1842–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Margulis A, Zhang W, Alt-Holland A, et al. E-cadherin suppression accelerates squamous cell carcinoma progressioin in three-dimensional, human tissue constructs. Cancer Res. 65:1783–1791.Google Scholar
  16. 16.
    Margulis A, Zhang W, Alt-Holland A, et al. Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinoma. Int J Cancer. 2006;118:821–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Franchi A, Gallo O, Boddi V, et al. Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination. Clin Cancer Res. 1996;2(10):1801–8.PubMedGoogle Scholar
  18. 18.
    Schipper JH, Frixen UH, Behrens J, et al. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991;51(23 Pt 1):6328–37.PubMedGoogle Scholar
  19. 19.
    Kawano T, Nakamura Y, Yanoma S, et al. Expression of E-cadherin, and CD44 s and CD44v6 and its association with prognosis in head and neck cancer. Auris Nasus Larynx. 2004;31(1):35–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Mannarini L, Kratochvil V, Calabrese L, et al. Human papilloma virus (HPV) in head and neck region: review of literature. Acta Otorhinolaryngol Ital. 2009;29(3):119–26.PubMedGoogle Scholar
  21. 21.
    Li S, Jiao J, Lu Z, Zhang M. An essential role for N-cadherin and beta-catenin for progression in tongue squamous cell carcinoma and their effect on invasion and metastasis of Tca8113 tongue cancer cells. Oncol Rep. 2009;21(5):1223–33.PubMedGoogle Scholar
  22. 22.
    Pyo SW, Hashimoto M, Kim YS, et al. Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome. J Craniomaxillofac Surg. 2007;35(1):1–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Bosch FX, Andl C, Abel U, et al. E-cadherin is a selective and strongly dominant prognostic factor in squamous cell carcinoma: a comparison of E-cadherin with desmosomal components. Int J Cancer. 2005;114(5):779–90.PubMedCrossRefGoogle Scholar
  24. 24.
    Foschini MP, Cocchi R, Morandi L, et al. E-cadherin loss and Delta Np73L expression in oral squamous cell carcinomas showing aggressive behavior. Head Neck. 2008;30(11):1475–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Al Moustafa AE, Foulkes WD, Benlimame N, et al. E6/E7 proteins of HPV type 16 and ErbB-2 cooperate to induce neoplastic transformation of primary normal oral epithelial cells. Oncogene. 2004;23(2):350–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Stenner M, Yosef B, Huebbers CU, et al. Nuclear translocation of beta-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression? Histopathology. 2011;58(7):1117–26.PubMedCrossRefGoogle Scholar
  27. 27.
    Muller S, Su L, Tighiouart M, et al. Distinctive E-cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma: predictive and prognostic correlation. Cancer. 2008;113(1):97–107.PubMedCrossRefGoogle Scholar
  28. 28.
    Liu LK, Jiang XY, Zhou XX, et al. Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome. Mod Pathol. 2010;23(2):213–24.PubMedCrossRefGoogle Scholar
  29. 29.
    Karayiannakis AJ, Syrigos KN, Alexiou D, et al. Expression patterns of the novel catenin p120cas in gastrointestinal cancers. Anticancer Res. 1999;19(5C):4401–5.PubMedGoogle Scholar
  30. 30.
    Ohkubo T, Ozawa M. p120(ctn) binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity. J Biol Chem. 1999;274(30):21409–15.PubMedCrossRefGoogle Scholar
  31. 31.
    Behrens J, Vakaet L, Friis R, et al. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol. 1993;120(3):757–66.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • O. C. Ukpo
    • 1
  • W. L. Thorstad
    • 2
  • Q. Zhang
    • 3
  • J. S. LewisJr.
    • 1
    • 4
  1. 1.Department of Pathology and Immunology, Division of Anatomic and Molecular PathologyWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Radiation OncologyWashington University School of MedicineSt. LouisUSA
  3. 3.Department of Preventative Medicine and Public Health, Division of BiostatisticsWashington University School of MedicineSt. LouisUSA
  4. 4.Department of Otolaryngology-Head and Neck SurgeryWashington University School of MedicineSt. LouisUSA

Personalised recommendations