Role of platelet derived growth factor receptor (PDGFR) over-expression and angiogenesis in ependymoma.

Abstract

New molecularly targeted therapies are needed for childhood ependymoma. Angiogenesis and the PDGFR pathway could be potential therapeutic targets. This study aimed to screen ependymomas for the expression and clinicopathological correlates of angiogenic factors and potential therapeutic targets including VEGFR, endoglin (CD105), CD34, CD31, c-Kit, PDGFR-α and PDGFR-β. Immunohistochemistry for angiogenesis factors and PDGFR-α and β was performed in 24 archival tumor samples from children and adults treated for ependymoma at our institution. CD31 density, CD105 density and pericyte coverage index (PCI) were calculated. These findings were correlated with clinical outcome. VEGFR2 was overexpressed in tumor cells in only one out of 24 cases, but was found overexpressed in the vessels in 6 cases. PDGFR-α and β were found to be over-expressed in the ependymoma tumor cells in seven out of 24 cases (29.2 %). CD31 density, CD105 density and PCI did not correlate with expression of PDGFRs. Overexpression of PDGFR-α and β in tumor cells and overexpression of PDGFR-α in tumor endothelium had prognostic significance and this was maintained in multivariate analysis for overexpression of PDGFR-α in tumor cells (2 year progression free survival was 16.7 ± 15.2 for cases with overexpression of PDGFR-α in the tumor vs. 74.5 ± 15.2 for those with low/no expression, hazard ratio = 5.78, p = 0.04). A number of angiogenic factors are expressed in ependymoma tumor cells and tumor endothelium. Preliminary evidence suggests that the expression of PDGFRs could have a prognostic significance in ependymoma. This data suggests that PDGFRs should be further evaluated as targets using novel PDGFR inhibitors.

• Authors: Lucas Moreno, Sergey Popov, Alexa Jury, Saffa Al Sarraj, Chris Jones, Stergios Zacharoulis
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 111 Issue 2 Pg. 169-76 (Jan 2013) ISSN: 1573-7373 [Electronic] United States
• PMID: 23135775 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Receptors, Platelet-Derived Growth Factor
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Adolescent
• Adult
• Antigens, CD (metabolism)
• Child
• Child, Preschool
• Disease-Free Survival
• Ependymoma (metabolism, mortality, physiopathology)
• Female
• Humans
• Infant
• Longitudinal Studies
• Male
• Middle Aged
• Neovascularization, Pathologic (etiology)
• Receptors, Platelet-Derived Growth Factor (metabolism)
• Retrospective Studies
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)