Authors: Lucas Moreno Sergey Popov Alexa Jury Saffa Al Sarraj Chris Jones Stergios Zacharoulis
Publish Date: 2012/11/08
Volume: 111, Issue: 2, Pages: 169-176
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 cKit PDGFRα and PDGFRβ Immunohistochemistry for angiogenesis factors and PDGFRα 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 PDGFRα and β were found to be overexpressed in the ependymoma tumor cells in seven out of 24 cases 292 CD31 density CD105 density and PCI did not correlate with expression of PDGFRs Overexpression of PDGFRα and β in tumor cells and overexpression of PDGFRα in tumor endothelium had prognostic significance and this was maintained in multivariate analysis for overexpression of PDGFRα in tumor cells 2 year progression free survival was 167 ± 152 for cases with overexpression of PDGFRα in the tumor vs 745 ± 152 for those with low/no expression hazard ratio = 578 p = 004 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 inhibitorsThis study was approved by The Royal Marsden NHS Foundation Trust Committee for Clinical Research CCR2935 protocol and conducted in compliance with the protocol local standard operative procedures and policies and Good Clinical Practice standards as required in the United Kingdom including the Research Governance Framework 2005 and other applicable regulatory requirements such as the Human Tissue Act 2004
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