Expression of bone morphogenetic proteins in human osteosarcoma. Immunohistochemical detection with monoclonal antibody

Cancer. 1994 Jan 1;73(1):85-91. doi: 10.1002/1097-0142(19940101)73:1<85::aid-cncr2820730116>3.0.co;2-8.

Abstract

Background: Bone morphogenetic proteins (BMP) induce ectopic bone formation in vivo and may play a role in normal bone development. In addition, bone morphogenetic activity, as measured in a bone-forming assay in immunodeficient, athymic nu/nu mice, is present in a proportion of osteosarcomas; this activity, which may be mediated by BMP, is correlated with a poor prognosis.

Methods: The development of a monoclonal antibody against recombinant human BMP-2, AbH3b2/17, has allowed immunohistochemical localization of BMP in tumor tissues. Cryostat sections of osteosarcomas (21 tumor samples), chondrosarcomas (5 samples), and Ewing's sarcomas of bone (5 samples) were examined with AbH3b2/17 using the avidin-biotin-immunoperoxidase method.

Results: The authors found AbH3b2/17 immunoreactivity in 12 of the 21 osteosarcoma samples (57% sensitivity) obtained from 20 patients. For one patient, samples of the primary lesion and a subsequent metastasis were tested, and only the latter showed AbH3b2/17 immunoreactivity. The chondrosarcomas and Ewing's sarcomas examined showed no immunoreactivity. In antigen-positive osteosarcomas, AbH3b2/17 immunostaining was localized predominantly in the cytoplasm of tumor cells. Moreover, the proportion of AbH3b2/17-reactive cells varied among osteosarcomas with disparate histologic features.

Conclusions: The authors identified a rapid and widely applicable method for detecting BMP expression in intact tissues, which may complement and enhance the bone-forming assay in nu/nu mice as a prognostic procedure in osteosarcomas.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / biosynthesis
  • Bone Morphogenetic Proteins
  • Bone Neoplasms / chemistry*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Child
  • Chondrosarcoma / chemistry
  • Chondrosarcoma / genetics
  • Chondrosarcoma / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Growth Substances / analysis*
  • Growth Substances / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Osteosarcoma / chemistry*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Osteosarcoma / secondary
  • Proteins / analysis*
  • Proteins / genetics
  • Sarcoma, Ewing / chemistry
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / pathology
  • Species Specificity
  • Staining and Labeling

Substances

  • Antibodies, Monoclonal
  • Bone Morphogenetic Proteins
  • Growth Substances
  • Neoplasm Proteins
  • Proteins