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Human Telomere Reverse Transcriptase Expression Predicts Progression and Survival in Pediatric Intracranial Ependymoma

Uri Tabori, Jing Ma, Michael Carter, Maria Zielenska, James Rutka, Eric Bouffet, Ute Bartels, David Malkin, Cynthia Hawkins

From the Divisions of Hematology/Oncology, Pathology and Neurosurgery, The Hospital for Sick Children and the University of Toronto, Toronto, Canada

Address reprint requests to Cynthia Hawkins, MD, PhD, Division of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8 Canada; e-mail: cynthia.hawkins{at}sickkids.ca

PURPOSE: 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.

PATIENTS AND 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 ( = 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.

CONCLUSION: 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.

Supported by a grant from BrainChild Canada, The Canadian Friends of Tel-Aviv University/Hospital for Sick Children Medical Exchange Program, and the Jonathon Hill Memorial Fund. C.H. is supported by a clinician-scientist award from Canadian Institutes of Health Reserach/Eli Lilly/Cancer Care Ontario.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.