title: Expression of HER2/erbB-2 correlates with survival in osteosarcoma.
abstract: OBJECTIVE
  In osteosarcoma, prognostic factors at diagnosis other than clinical stage have not been clearly identified. The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival.
  
  
  METHODS
  We performed a retrospective immunohistochemical study on material obtained from patients treated on the Memorial Sloan-Kettering Cancer Center T12 protocol between 1986 and 1993. Paraffin-embedded tissue was identified from 53 patients (73% of patients enrolled onto protocol) and stained for HER2/erbB-2, p53, and p-glycoprotein expression using standard monoclonal antibodies and methods.
  
  
  RESULTS
  At the time of initial biopsy, 20 (42.6%) of 47 samples demonstrated high levels of HER2/erbB-2 expression. Higher frequencies of expression were observed in samples from patients with metastatic disease at presentation and at the time of relapse. Expression of HER2/erbB-2 correlated with a significantly worse histologic response (P =.03). In patients presenting with nonmetastatic disease, expression of HER2/erbB-2 at the time of initial biopsy was associated with a significantly decreased event-free survival (47% v 79% at 5 years, P =.05). p53 and p-glycoprotein expression did not correlate with histologic response or patient event-free survival.
  
  
  CONCLUSIONS
  The correlation of HER2/erbB-2 expression with histologic response to preoperative chemotherapy and event-free survival in this study suggests that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator. The correlation also suggests that clinical trials of antibodies that target this receptor, such as recombinant humanized anti-HER2 monoclonal antibody (Herceptin; Genentech, San Francisco, CA), should be considered for the treatment of osteosarcoma.
authors.affiliation: Departments of Pediatrics, Pathology, Epidemiology and Biostatistics, Surgery, Orthopaedic Service, and Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gorlick
authors.forename: A G
authors.initials: AG
authors.lastname: Huvos
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: A
authors.initials: A
authors.lastname: Aledo
authors.forename: G P
authors.initials: GP
authors.lastname: Beardsley
authors.forename: J H
authors.initials: JH
authors.lastname: Healey
authors.forename: P A
authors.initials: PA
authors.lastname: Meyers
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53