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Updated: Jun 21, 2026

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma
Ayesha Abdeen1, Alexander J Chou, John H Healey
1Department of Orthopaedic Surgery, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY, USA.
Background:
Multiple cell-signaling ligands and receptors-including vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), endothelial growth factor (EGF), v-akt murine thymoma viral oncogene homolog (AKT), platelet-derived growth factor (PDGF), mitogen-activated protein kinase (MAPK), and 70-kilodalton (kD) protein S6 kinase (p70S6 kinase)-reportedly are variably expressed in osteogenic sarcoma. Expression of these proteins may have future implications for prognostication and targeted therapy. The objective of the current study was to determine the relation between clinical outcome and the expression of these proteins.
Methods:
A paraffin-embedded microarray of 48 human osteogenic sarcoma tissue specimens was stained with the antibodies against VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase. Staining for each protein included the total protein and, when applicable, the phosphorylated version of the protein. Immunohistochemical staining was then correlated with patient survival (overall survival [OS] and event-free survival [EFS]), histologic response to chemotherapy, and serum markers.
Results:
There was a negative correlation between VEGF receptor 3 (VEGF-R3) and both OS and EFS. VEGF-B was correlated with a poor histologic response to chemotherapy. Serum markers were not correlated with any specific proteins. When using a P value of .05, multiple correlations were observed between proteins of various pathways.
Conclusions:
The current results suggested that the VEGF pathway is a critical signaling pathway in osteogenic sarcoma. These data have identified specific proteins within these pathways toward which future investigations should be directed to further clarify their prognostic potential.
Insights
Vascular Endothelial Growth Factor Receptor 3 (VEGF-R3) expression negatively correlates with osteosarcoma patient survival. VEGF-B indicates a poor response to chemotherapy, highlighting the VEGF pathway's role in osteosarcoma progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteogenic sarcoma exhibits variable expression of key cell-signaling proteins like VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase.
- These protein expressions may hold future significance for osteosarcoma prognostication and targeted therapeutic strategies.
- The study aimed to investigate the correlation between the expression of these proteins and clinical outcomes in osteosarcoma patients.
Purpose of the Study:
- To determine the relationship between the expression of specific cell-signaling proteins and clinical outcomes in osteogenic sarcoma.
- To identify potential prognostic markers within the investigated signaling pathways.
- To explore the role of these proteins in predicting patient survival and response to chemotherapy.
Main Methods:
- Utilized a paraffin-embedded tissue microarray of 48 human osteogenic sarcoma specimens.
- Performed immunohistochemical staining for VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase (total and phosphorylated forms).
- Correlated protein expression with overall survival (OS), event-free survival (EFS), histologic response to chemotherapy, and serum markers.
Main Results:
- A negative correlation was observed between VEGF receptor 3 (VEGF-R3) expression and both OS and EFS.
- VEGF-B expression was associated with a poor histologic response to chemotherapy.
- Multiple correlations were found between proteins from various signaling pathways (P < .05), while serum markers showed no significant correlation with specific proteins.
Conclusions:
- The VEGF signaling pathway appears to be critically involved in osteogenic sarcoma.
- Specific proteins within the VEGF pathway demonstrate prognostic potential.
- Further investigations are warranted to elucidate the prognostic value of these identified proteins in osteosarcoma.
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