Clinical & Experimental Metastasis

, Volume 32, Issue 1, pp 55–63 | Cite as

Epithelial-mesenchymal transition (EMT) markers have prognostic impact in multiple primary oral squamous cell carcinoma

  • Sabrina Daniela da SilvaEmail author
  • Grégoire B. Morand
  • Faisal A. Alobaid
  • Michael P. Hier
  • Alex M. Mlynarek
  • Moulay A. Alaoui-Jamali
  • Luiz Paulo Kowalski
Research Paper


Multiple primary tumors can occur in up to 35 % of the patients with head and neck cancer, however its clinicopathological features remain controversial. Deregulation of epithelial-mesenchymal transition (EMT) signaling has been associated with aggressive malignancies and tumor progression to metastasis in several cancer types. This study is the first to explore EMT process in multiple primary oral squamous cell carcinomas (OSCC). Immunohistochemical analysis of E-cadherin, catenin (α, β, and γ), APC, collagen IV, Ki-67, cyclin D1, and CD44 were performed in a tissue microarray containing multiple representative areas from 102 OSCC patients followed-up by at least 10 years. Results were analysed in relation to clinicopathological characteristics and survival rates in patients presenting multiple primary tumors versus patients without second primary tumors or metastatic disease. Significant association was observed among multiple OSCCs and protein expression of E-cadherin (P = 0.002), β-catenin (P = 0.047), APC (P = 0.017), and cyclin D1 (P = 0.001) as well as between lymph nodes metastasis and Ki-67 staining (P = 0.021). OSCCs presenting vascular embolization were associated with negative β-catenin membrane expression (P = 0.050). There was a significantly lower survival probability for patients with multiple OSCC (log-rank test, P < 0.0001), for tumors showing negative protein expression for E-cadherin (log-rank test, P = 0.003) and β-catenin (log-rank test, P = 0.031). Stratified multivariate survival analysis revealed a prognostic interdependence of E-cadherin and β-catenin co-downexpression in predicting the worst overall survival (log-rank test, P = 0.007). EMT markers have a predicted value for invasiveness related to multiple primary tumors in OSCC and co-downregulation of E-cadherin and β-catenin has a significant prognostic impact in these cases.


Multiple primaries Oral cancer Epithelial-mesenchymal transition Recurrence Metastasis 



This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 06/61039-8 and CEPID/FAPESP 98/14335). GBM is supported by the Swiss Cancer League, Effingerstrasse 40, 3001 Bern, Switzerland (BIL KFS-3002-08-2012). The authors would like to acknowledge José Ivanildo Neves, Carlos Ferreira Nascimento, and Severino Ferreira for their technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Sabrina Daniela da Silva
    • 1
    • 2
    • 3
    Email author
  • Grégoire B. Morand
    • 1
    • 2
  • Faisal A. Alobaid
    • 1
  • Michael P. Hier
    • 1
  • Alex M. Mlynarek
    • 1
  • Moulay A. Alaoui-Jamali
    • 2
  • Luiz Paulo Kowalski
    • 3
  1. 1.Department of Otolaryngology-Head and Neck Surgery, Sir Mortimer B. Davis-Jewish General Hospital, Segal Cancer Centre and Lady Davis Institute for Medical ResearchMcGill UniversityMontrealCanada
  2. 2.Departments of Medicine, Oncology, and Pharmacology and Therapeutics, Faculty of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, Segal Cancer Centre and Lady Davis Institute for Medical ResearchMcGill UniversityMontrealCanada
  3. 3.Department of Head and Neck Surgery and OtorhinolaryngologyA. C. Camargo Cancer Center and National Institute of Science and Technology on Oncogenomics (INCITO)São PauloBrazil

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