Expression of HER2/erbB-2 correlates with survival in osteosarcoma

J Clin Oncol. 1999 Sep;17(9):2781-8. doi: 10.1200/JCO.1999.17.9.2781.


Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adolescent
  • Adult
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Neoplasm Proteins / metabolism*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2