title: ErbB2 expression is correlated with increased survival of patients with osteosarcoma.
abstract: BACKGROUND
  Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high-grade osteosarcoma.
  
  
  METHODS
  ErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed-up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event-free and overall survival.
  
  
  RESULTS
  Of the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07-4.72 and 1.09-5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells.
  
  
  CONCLUSIONS
  In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival. Further data are needed before this marker can be used in making clinical decisions.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Akatsuka
authors.forename: Takuro
authors.initials: T
authors.lastname: Wada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kokai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawaguchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Isu
authors.forename: Katsushige
authors.initials: K
authors.lastname: Yamashiro
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamawaki
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ishii
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases