Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification

J Pediatr Hematol Oncol. 2003 Jan;25(1):27-32. doi: 10.1097/00043426-200301000-00007.


The purpose of this study was to investigate whether Her-2/neu expression at diagnosis of osteosarcoma could provide biologic and prognostic information that predicts the risk of pulmonary metastases and outcome. Human epidermal growth factor (Her-2/neu) expression in 25 initial pretreatment osteosarcoma biopsies and 12 posttreatment pulmonary metastatic osteosarcoma resection specimens was assessed by standard immunohistochemical techniques on formalin-fixed paraffin-embedded tissue. As a screening analysis to determine if gene amplification may be a mechanism for increased Her-2/neu expression, FISH analysis was conducted on seven Her-2/neu immunostain-positive samples and five Her-2/neu immunostain-negative samples. Cytoplasmic Her-2/neu reactivity was identified in 11/25 (44%) of primary tumors and in 7/12 (58%) resection specimens from pulmonary metastases. Cytoplasmic Her-2/neu expression was associated with shorter overall metastasis-free survival. Her-2/neu gene amplification was identified by FISH analysis in six of the seven immunostain-positive samples but was also identified in two of the five immunostain-negative samples. Her-2/neu expression in patients with osteosarcoma is associated with an increased risk of metastasis and may define a subset of patients with a more aggressive tumor phenotype. Her-2/neu gene amplification may provide a mechanism for Her-2/neu overexpression in certain cases of osteosarcoma. Whether Her-2/neu expression influences outcome needs to be examined further in a prospective fashion. The hope is that Her-2/neu expression will identify patients who may benefit from the addition of directed biologic therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Child
  • Female
  • Gene Amplification*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Male
  • Osteosarcoma / metabolism*
  • Osteosarcoma / secondary
  • Pilot Projects
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Risk Factors
  • Survival Rate
  • Up-Regulation


  • Receptor, ErbB-2