title: Cooverexpression of ERBB1 and ERBB4 receptors predicts poor clinical outcome in pN+ oral squamous cell carcinoma with extranodal spread.
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.
authors: Department of Otolaryngology-Head and Neck Surgery - Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, QC, Canada, sabrinadaniela@hotmail.com.
authors: Sabrina Daniela
authors: SD
authors: Silva
authors: Moulay A
authors: MA
authors: Alaoui-Jamali
authors: Michael
authors: M
authors: Hier
authors: Fernando Augusto
authors: FA
authors: Soares
authors: Edgard
authors: E
authors: Graner
authors: Luiz Paulo
authors: LP
authors: Kowalski
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D018739:Oncogene Proteins v-erbB / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D066247:Receptor, ErbB-4; D016896:Treatment Outcome
chemical_list: D066246:ErbB Receptors; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D018739:Oncogene Proteins v-erbB; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human