Clinical and molecular stratification of disease risk in medulloblastoma

The accurate assessment of disease risk among children with medulloblastoma remains a major challenge to the field of paediatric neuro-oncology. In th e current study we investigated the capacity of molecular abnormalities to increase the accuracy of disease risk stratification above that afforded by clinical staging alone. 41 primary medulloblastoma tumour samples were ana lysed for ErbB2 receptor expression using immunohistochemistry, and for abe rrations of chromosome 17 and amplification of the MYC oncogene using fluor escence in situ hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and 49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in association with gain of 17q (29%), compatible wi th an isochromosome of 17q. Amplification of MYC was detected in only 2 tum ours. Significant prognostic factors included, 'metastatic disease' (P = 0. 0006), 'sub-total tumour resection' (P = 0.007), 'high ErbB2 receptor expre ssion' (P = 0.003) and 'isolated 17p loss' (P = 0.003). Combined analysis o f clinical and molecular factors enabled greater resolution of disease risk than clinical factors alone, identifying a sub-population of patients with particularly favourable disease outcome. These data support the hypothesis that a combination of clinical and molecular factors may afford a more rel iable means of assigning disease risk in patients with medulloblastoma, the reby providing a more accurate basis for targeting therapy in children with this disease. (C) 2001 Cancer Research Campaign.