Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas.
OBJECTIVE
We previously showed that overexpression of epidermal growth factor receptor (EGFR) is associated with malignant grade in childhood glioma. The objective of this study was to determine whether protein expression of EGFR or platelet-derived growth factor receptor (PDGFR) and their active signaling pathways are related to malignant histology, progression of disease, and worse survival.


METHODS
Tissue microarrays were prepared from untreated tumors from 85 new glioma patients [22 high-grade gliomas (HGG) and 63 low-grade gliomas (LGG)] diagnosed at this institution from 1989 to 2004. Immunohistochemistry was used to assess total expression of EGFR, PDGFR beta, and PTEN and expression of phosphorylated EGFR, phosphorylated PDGFR alpha (p-PDGFR alpha), phosphorylated AKT, phosphorylated mitogen-activated protein kinase, and phosphorylated mammalian target of rapamycin. These results were correlated with clinicopathologic data, including extent of initial tumor resection, evidence of dissemination, tumor grade, proliferation index, and survival, as well as with Affymetrix gene expression profiles previously obtained from a subset of these tumors.


RESULTS
High expression of p-PDGFR alpha, EGFR, PDGFR beta, and phosphorylated EGFR was seen in 85.7%, 80.0%, 78.9%, and 47.4% of HGG and 40.0%, 87.1%, 41.7%, and 30.6% of LGG, respectively. However, high expression of p-PDGFR alpha and PDGFR beta was the only significant association with malignant histology (P = 0.031 and 0.005, respectively); only the loss of PTEN expression was associated with worse overall survival. None of these targets, either alone or in combination, was significantly associated with progression-free survival in either LGG or HGG.


CONCLUSIONS
High PDGFR protein expression is significantly associated with malignant histology in pediatric gliomas, but it does not represent an independent prognostic factor. Deficient PTEN expression is associated with worse overall survival in HGG.
Division of Hematology-Oncology, Children's National Medical Center, 4th Floor West Wing, 111 Michigan Avenue, Northwest, Washington, DC 20010, USA.
Halldora K
HK
Thorarinsdottir
Mariarita
M
Santi
Robert
R
McCarter
Elisabeth J
EJ
Rushing
Robert
R
Cornelison
Alessandra
A
Jales
Tobey J
TJ
MacDonald
D000293:Adolescent; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D011379:Prognosis; D040081:Protein Array Analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D046888:Tissue Array Analysis
D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human