title: Epidermal growth factor receptor gene copy number aberration at the primary tumour is significantly associated with extracapsular spread in oral cancer.
abstract: BACKGROUND
  Extracapsular spread (ECS) of lymph node metastasis in head and neck cancers, including oral squamous cell carcinomas (OSCCs), is known to reflect tumour aggressiveness, and is significantly associated with high rates of loco-regional recurrence, distant metastasis, and poor outcome. The purpose of this study was to confirm ECS as an important prognostic indicator and to determine the significant factors associated with ECS in OSCCs.
  
  
  METHODS
  We investigated the incidence of ECS and impact of ECS on survival in 127 OSCC patients. To determine the factors significantly correlated with ECS, we examined many factors, including the clinicopathological features of primary tumours, lymph node metastasis, and copy number aberrations of the cyclin D1 gene (CCND1) and epidermal growth factor receptor gene (EGFR) at primary tumours, and evaluated the value of predicting the risk of ECS of the metastatic lymph node.
  
  
  RESULTS
  Kaplan-Meier and multivariate disease-free and overall survival analysis clearly demonstrated that ECS is an independent prognostic factor in OSCCs. Moreover, logistic regression analysis showed that the number of pathologically positive nodes and copy number aberrations of EGFR at the primary tumour are independent predictors of ECS.
  
  
  CONCLUSIONS
  The findings suggest that ECS is an independent prognostic factor in OSCCs. Moreover, the number of pathologically positive lymph nodes and EGFR numerical aberrations of the primary tumour were also shown to be excellent predictors of ECS in OSCCs. Preoperative evaluation of EGFR numerical aberrations might therefore be a useful tool for selecting patients at high risk of ECS, who would benefit from targeted aggressive multimodality therapy.
authors.affiliation: Maxillofacial Surgery, Maxillofacial Reconstruction and Function, Division of Maxillofacial and Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Michikawa
authors.forename: N
authors.initials: N
authors.lastname: Uzawa
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Ohyama
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Amagasa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D018628:Gene Dosage; D018773:Genes, erbB-1; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis; D011379:Prognosis