Vascularity and angiogenesis as predictors of growth in optic pathway/hypothalamic gliomas.
OBJECTIVE
The authors' aim in conducting this study was to investigate retrospectively the prognostic significance of angiogenic features in optic pathway/hypothalamic gliomas (OPHGs) in children.


METHODS
Patients were identified in whom a diagnosis of OPHG was made using pathological analysis at the Toronto Hospital for Sick Children between 1985 and 2002. Tumor specimens were reviewed for diagnostic accuracy and adequacy of the specimen. Sections were immunostained with factor VIII to assess microvessel density (MVD). A ratio of alpha-smooth muscle actin to factor VIII immunostaining was calculated to arrive at a vascular maturity index (VMI). Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) immunostaining were performed to evaluate angiogenic factors. In addition, the MIB-1 labeling index (LI) was used to assess proliferation. These factors were evaluated with respect to progression-free survival (PFS). Forty-one of 60 patients originally identified had adequate samples and follow up for inclusion in the study. Of these, eight patients had coexisting neurofibromatosis Type 1. Twenty-eight patients experienced tumor progression after the initial treatment (surgery with or without adjuvant treatment). Thirty-eight patients are still alive. A high MVD (> 21 vessels/1.2 mm2) was associated with a significantly higher rate of progression compared with a low MVD (< 21 vessels/1.2 mm2; p = 0.017). Microvessel density was also predictive of reduced PFS on multivariate analysis stratified for extent of resection (p = 0.04), and VMI as well as intensity and distribution of VEGF and VEGFR staining and the MIB-1 LI were not significantly associated with PFS.


CONCLUSIONS
These findings suggest that MVD is the best current predictor of PFS in incompletely resected OPHGs. This information highlights the importance of angiogenesis in regard to low-grade gliomas.
Bartels
Ute
U
Division of Hematology/Oncology, Pediatric Brain Tumor Program, The Hospital for Sick Children, Toronto, Ontario, Canada. ute.bartels@sickkids.ca
Hawkins
Cynthia
C
Jing
Ma
M
Ho
Michael
M
Dirks
Peter
P
Rutka
James
J
Stephens
Derek
D
Bouffet
Eric
E
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D007124:Immunoenzyme Techniques; D007223:Infant; D008833:Microcirculation / Q000473:pathology; D018365:Neoplasm, Residual / Q000098:blood supply / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000601:surgery; D020339:Optic Nerve Glioma / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies
D014408:Biomarkers, Tumor