Histopathological prognostic factors in medulloblastoma: High expression of survivin is related to unfavourable outcome☆
Introduction
Medulloblastoma is the most common malignant primary brain tumour in children. Therapy of medulloblastoma comprises maximal surgical resection of the tumour followed by craniospinal irradiation and chemotherapy. Such treatment causes long-term morbidity including endocrine and growth disturbances, as well as neurocognitive impairment, which is particularly severe in young children.1
Currently, patients are stratified into different therapy arms based on clinical parameters such as patient age, metastatic stage, and residual tumour size. These clinical prognostic parameters are used to distinguish between a group of high- and average- risk patients.2 Yet, within the average risk group, clinical parameters do not identify a group of patients with a particular low risk of tumour recurrence, which could be treated with a substantially less toxic treatment regime as compared to standard treatment. Thus the major goal in the treatment of children with medulloblastoma is to identify patients who can be cured with a less toxic therapy while developing new treatment strategies for patients with a high risk of tumour recurrence. To this end biological markers are needed which (1) provide prognostic information and (2) serve as molecular targets for new treatment strategies.
Different prognostic parameters have been described in medulloblastoma (reviewed in Ref. [3]). In recent studies histopathological subtype,4, 5, 6 erbB-2,7 TRKC,8 and survivin9, 10 have been reported as prognostic factors for patient outcome. However, so far none of these parameters are used in clinical management for therapy stratification. An essential prerequisite for translation of prognostic and predictive parameters into clinical practice is validation of their prognostic influence by independent investigators.
We analysed the prognostic impact of histopathological subtype, expression of erbB-2, TRKC, and survivin in a cohort of Austrian medulloblastoma patients operated on between 1990 and 2004 and treated according to consecutive HIT therapy protocols.
Section snippets
Patients
Selection criteria for patients in this study were newly diagnosed medulloblastoma, operated on between 1990 and 2004 in Austria (Vienna, Graz, Linz, Salzburg, Innsbruck, and Klagenfurt); age at operation < 22 years, and randomisation into the consecutive multicentre trials (HIT) for medulloblastoma of the German Society of Paediatric Haematology and Oncology (GPOH).11, 12 Using these criteria, 126 patients were identified. No tumour tissue was available in 34 patients. Five tumours had other
Histopathology
Nuclear immunohistochemical expression of INI protein was detectable in all tumours, thus cases of AT/RT mimicking morphological features of medulloblastoma were not included in the investigated sample.
Discussion
In the present study we analysed the prognostic impact of four histopathological parameters on patient survival in a series of 82 medulloblastoma patients treated according to the consecutive HIT therapy protocols. Among the analysed factors, only high expression of survivin was related to poor outcome. Histopathological subtype, erbB-2, and TRKC expression in medulloblastoma have been analysed in several previous studies. However, contradictory results about the prognostic impact of these
Conflict of interest statement
None declared.
Acknowledgements
We thank Mrs E. Dirnberger, Mrs C. Karner, and Mrs H. Flicker for excellent technical assistance. Mrs G. Pammer, Mrs S. Schemel, Dr. K. Triebl, Dr. R. Prühlinger, Dr. A. Gamper, Dr. A. Gupper, and Dr. J. Trenkler for retrieval of clinical data and Dr. P. Pilz, Dr. A. Reiner-Concin, and Dr. W. Feichtinger for providing biopsy material.
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A cooperative study of the Austrian Neurooncology Network (ANN).