1. ¹Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
2. ²Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Addenbrooke's Hospital, Box 231, Cambridge CB2 2QQ, UK

Correspondence: Dr LM Bäcklund, E-mail: Magnus.Backlund@onkpat.ki.se

Received 26 January 2005; Revised 6 May 2005; Accepted 18 May 2005; Published online 21 June 2005.

Abstract

Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most common and most malignant type of adult CNS tumour. Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value. The survival data on 37 carefully sampled AA was correlated with the results of a detailed analysis of the status of nine genes known to be involved in the development of astrocytic tumours. These included three genes coding for proteins in the p53 pathway (TP53, p14^ARFand MDM2), four in the Rb1 pathway (CDKN2A, CDKN2B, RB1 and CDK4) and PTEN and EGFR. We found that loss of both wild-type copies of any of the three tumour suppressor genes CDKN2A, CDKN2B and RB1 or gene amplification of CDK4, disrupting the Rb1 pathway, were associated with shorter survival (P=0.009). This association was consistent in multivariate analysis, including adjustment for age (P=0.013). The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.