Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions.
This study aims to investigate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in giant cell tumor of bone (GCT) and other osteolytic lesions in bone. By using semi-quantitative RT-PCR, we showed that three major isoforms of VEGF (121, 165 and 189) were expressed in GCTs, with isoform 121 being the most abundant. The expression levels of VEGF and MMP-9 mRNA were significantly higher in advanced GCTs (stage II/III) than in stage I GCTs. We further elucidated the cellular localization of VEGF and MMP-9 gene transcripts in GCT and other osteolytic lesions using an in situ hybridization assay. The results showed that stromal tumor cells and osteoclast-like giant cells of GCT, fibrous stromal cells in anuerysmal bone cysts and fibrous dysplasia, and Langerhans-type giant cells as well as histocytes in eosinophillic granuloma, were all strongly positive for VEGF and MMP-9 mRNA expression. In a prospective study, we performed VEGF and MMP-9 immuno-staining on paraffin sections of pathological tissues harvested from 48 patients (14 GCT, 10 anuerysmal bone cysts, 10 eosinophillic granuloma, 4 fibrous dysplasia, 2 simple bone cyst, 2 osteomyelitis and 6 patients with fractured femoral head as control). The results showed that the differences in VEGF and MMP-9 expression between Stage I and other advanced Stages (II, III and recurrent) were highly significant (p<0.001), with advanced stages showing a higher mean expression. The difference between recurrent and Stage II and III lesions, was also statistically significant (p=0.03 for VEGF, and p=0.01 for MMP-9 expression), with recurrent lesions showing a higher mean expression of both VEGF and MMP-9. In conclusion, VEGF and MMP-9 expression in osteolytic lesions of bone co-relates well with the extent of bone destruction and local recurrence. Their expression may therefore provide some prognostic indication of the possible aggressive behavior of the underlying pathology.
Kumta
S M
SM
Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T. Hongkong, China. kumta@cuhk.edu.hk
Huang
L
L
Cheng
Y Y
YY
Chow
L T C
LT
Lee
K M
KM
Zheng
M H
MH
D001845:Bone Cysts / Q000378:metabolism; D017824:Bone Cysts, Aneurysmal / Q000378:metabolism; D001859:Bone Neoplasms / Q000737:chemistry* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D005357:Fibrous Dysplasia of Bone / Q000378:metabolism; D015870:Gene Expression; D018212:Giant Cell Tumor of Bone / Q000737:chemistry* / Q000473:pathology; D006099:Granuloma / Q000378:metabolism; D006644:Histiocytes / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010010:Osteoclasts / Q000737:chemistry; D010014:Osteolysis / Q000378:metabolism*; D010019:Osteomyelitis / Q000378:metabolism; D011446:Prospective Studies; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020780:Matrix Metalloproteinase 9