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Cooverexpression of ERBB1 and ERBB4 receptors predicts poor clinical outcome in pN+ oral squamous cell carcinoma with extranodal spread

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Abstract

Overexpression of members of the ErbB receptor family is common in oral squamous cell carcinomas (OSCC); however, their prognostic value for aggressive OSCC has been debated. Extranodal spread to cervical lymph nodes is the most significant prognostic indicator in OSCC. In the present study, we investigated the clinical significance of single versus paired overexpression of members of the ErbB receptor family in 82 OSCC patients with lymph nodes metastasis, with or without capsular rupture (CR) followed by at least 10 years. Immunohistochemistry analysis revealed a common overexpression of ErbB1 (P = 0.021), ErbB2 (P = 0.001), ErbB4 (P = 0.048), as well as MMP-2 (P = 0.043) in OSCC cases with CR+. Increased expression of ErbB1 was associated with MMP-2 in tumors with advanced clinical stages, including poorly differentiated (grade III) tumors (P < 0.050). Vascular embolization was associated with MMP-2 (P = 0.021) and MMP-13 (P = 0.010) overexpression. Survival analysis revealed a lower survival probability in tumors overexpressing ErbB1 (P = 0.038), ErbB4 (P = 0.043), and MMP-12 (P = 0.050). As well a strong association was observed in cases with high risk of recurrence and strong immunostaining for ErbB1 (P = 0.017), ErbB4 (P = 0.008), MMP-1 (P = 0.003), MMP-2 (P = 0.016), MMP-10 (P = 0.041), and MMP-13 (P = 0.005). Stratified multivariate survival analysis revealed a strong prognostic interdependence of ErbB1 and ErbB4 cooverexpression in predicting the worst overall and disease-free survivals (P = 0.0013 and P = 0.0004, respectively). Taken together, these results support a cooperation of ErbB1, ErbB4, and members of the MMP family in predicting OSCC invasion and poor clinical outcomes.

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Acknowledgments

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 06/61039-8 and CEPID/FAPESP 98/14335). Silva SD was supported by a FAPESP fellowship (06/61040-6). 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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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery - Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada

    Sabrina Daniela Silva & Michael Hier

  2. Departmens of Medicine and Oncology, and Lady Davis Institute for Medical Research and Segal Cancer Centre of the Jewish General Hospital, McGill University, Montreal, QC, Canada

    Sabrina Daniela Silva & Moulay A. Alaoui-Jamali

  3. Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil

    Sabrina Daniela Silva & Luiz Paulo Kowalski

  4. Department of Anatomic Pathology A.C. Camargo Cancer Center and Faculty of Dentistry, University of São Paulo, São Paulo, SP, Brazil

    Fernando Augusto Soares

  5. Department of Oral Diagnosis, School of Dentistry of Piracicaba, University of Campinas (UNICAMP), Piracicaba, SP, Brazil

    Edgard Graner

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  1. Sabrina Daniela Silva
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  2. Moulay A. Alaoui-Jamali
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Correspondence to Sabrina Daniela Silva.

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Silva, S.D., Alaoui-Jamali, M.A., Hier, M. et al. Cooverexpression of ERBB1 and ERBB4 receptors predicts poor clinical outcome in pN+ oral squamous cell carcinoma with extranodal spread. Clin Exp Metastasis 31, 307–316 (2014). https://doi.org/10.1007/s10585-013-9629-y

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