Human telomere reverse transcriptase expression predicts progression and survival in pediatric intracranial ependymoma.
OBJECTIVE
Pediatric intracranial ependymomas are a heterogeneous group of neoplasms with unpredictable clinical and biologic behavior. As part of ongoing studies to identify potential biologic and therapeutic markers, we analyzed the role of human telomere reverse transcriptase (hTERT; the catalytic subunit of telomerase) expression as a prognostic marker for this disease.


METHODS
Primary intracranial ependymomas that were resected at our institution between 1986 and 2004 were identified through the pathology and oncology databases. A tissue array was constructed from the patient samples and hTERT expression was evaluated by immunohistochemistry. Twenty-one samples were also analyzed for telomerase activity (telomerase repeat amplification protocol assay).


RESULTS
Eighty-seven tumors from 65 patients were analyzed. Five-year progression-free survival was 57% (SEM, 12%) and 21% (SEM, 8%) for hTERT-negative and hTERT-positive tumors, respectively (P = .002). Five-year overall survival was 84% (SEM, 7%) and 41% (SEM, 7%) for hTERT-negative and hTERT-positive tumors, respectively (P = .001). There was good correlation between telomerase activity and hTERT expression (kappa = 0.637). Multivariate analysis revealed hTERT expression to be the single most important predictor of survival of all known pathologic, clinical, and treatment factors (hazard ratio, 60.4; 95% CI, 6.4 to 561). All four patients with hTERT-negative tumors at relapse are still alive, with median follow-up of 11.2 years.


CONCLUSIONS
In this study, hTERT expression was the strongest predictor of outcome and was independent of other clinical and pathologic prognostic markers. It represents a simple and reliable biologic prognostic factor for intracranial ependymomas. These results should be confirmed in larger prospective trials.
Division of Hematology/Oncology, The Hospital for Sick Children and the University of Toronto, Toronto, Canada.
Uri
U
Tabori
Jing
J
Ma
Michael
M
Carter
Maria
M
Zielenska
James
J
Rutka
Eric
E
Bouffet
Ute
U
Bartels
David
D
Malkin
Cynthia
C
Hawkins
D000293:Adolescent; D000367:Age Factors; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000032:analysis*; D018450:Disease Progression; D004806:Ependymoma / Q000737:chemistry* / Q000401:mortality; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012307:Risk Factors; D019098:Telomerase / Q000032:analysis*
D004268:DNA-Binding Proteins; D019098:Telomerase