Expression of bone morphogenetic proteins in human osteosarcoma. Immunohistochemical detection with monoclonal antibody.
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.
Yoshikawa
H
H
Ludwig Institute for Cancer Research, New York Unit, New York.
Rettig
W J
WJ
Takaoka
K
K
Alderman
E
E
Rup
B
B
Rosen
V
V
Wozney
J M
JM
Lane
J M
JM
Huvos
A G
AG
Garin-Chesa
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D019485:Bone Morphogenetic Proteins; D001859:Bone Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D002648:Child; D002813:Chondrosarcoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D012516:Osteosarcoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D013045:Species Specificity; D013194:Staining and Labeling
D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D006133:Growth Substances; D009363:Neoplasm Proteins; D011506:Proteins