Elsevier

European Journal of Cancer

Volume 42, Issue 17, November 2006, Pages 2996-3003
European Journal of Cancer

Histopathological prognostic factors in medulloblastoma: High expression of survivin is related to unfavourable outcome

https://doi.org/10.1016/j.ejca.2006.05.038Get rights and content

Abstract

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma.

We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome.

Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome.

Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.

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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