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

Autor(es)

Silva, Sabrina Daniela ^{[1, 2, 3, 4, 5, 6]} ; Alaoui-Jamali, Moulay A. ^{[2, 3, 4, 5]} ; Hier, Michael ^[6] ; Soares, Fernando Augusto ^{[7, 8]} ; Graner, Edgard ^[9] ; Kowalski, Luiz Paulo ^[1]

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[2] McGill Univ, Dept Med, Montreal, PQ - Canada

^[3] McGill Univ, Dept Oncol, Montreal, PQ - Canada

^[4] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ - Canada

^[5] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ H3T 1E2 - Canada

^[6] McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Otolaryngol Head & Neck Surg, Montreal, PQ - Canada

^[7] Univ Sao Paulo, Fac Dent, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Dept Anat Pathol, AC Camargo Canc Ctr, Sao Paulo - Brazil

^[9] Univ Campinas UNICAMP, Sch Dent Piracicaba, Dept Oral Diag, Piracicaba, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL & EXPERIMENTAL METASTASIS; v. 31, n. 3, p. 307-316, MAR 2014.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 06/61039-8 - Identificacao de marcadores moleculares de progressao e prognostico em carcinomas epidermoides de boca.
• Beneficiário: Luiz Paulo Kowalski
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/61040-6 - Identificacao de marcadores moleculares de progressao e prognostico em carcinomas epidermoides de boca.
• Beneficiário: Sabrina Daniela da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado