No conflicts of interest were declared.
Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics†
Article first published online: 6 JAN 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 218, Issue 1, pages 86–94, May 2009
How to Cite
Fattet, S., Haberler, C., Legoix, P., Varlet, P., Lellouch-Tubiana, A., Lair, S., Manie, E., Raquin, M.-A., Bours, D., Carpentier, S., Barillot, E., Grill, J., Doz, F., Puget, S., Janoueix-Lerosey, I. and Delattre, O. (2009), Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics. J. Pathol., 218: 86–94. doi: 10.1002/path.2514
- Issue published online: 3 APR 2009
- Article first published online: 6 JAN 2009
- Accepted manuscript online: 6 JAN 2009 12:00AM EST
- Manuscript Accepted: 20 DEC 2008
- Manuscript Revised: 24 NOV 2008
- Manuscript Received: 18 SEP 2008
- CTNNB1 mutation;
- chromosome 6 deletion;
- array CGH;
- expression profile;
Medulloblastoma is the most frequent malignant paediatric brain tumour. The activation of the Wnt/β-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favourable patient outcome. We report a series of 72 paediatric medulloblastomas evaluated for β-catenin protein expression, CTNNB1 mutations, and comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of β-catenin showed extensive nuclear staining (>50% of the tumour cells) in six cases and focal nuclear staining (<10% of cells) in three cases. The other cases either exhibited a signal strictly limited to the cytoplasm (58 cases) or were negative (five cases). CTNNB1 mutations were detected in all β-catenin extensively nucleopositive cases. The expression profiles of these cases documented strong activation of the Wnt/β-catenin pathway. Remarkably, five out of these six tumours showed a complete loss of chromosome 6. In contrast, cases with focal nuclear β-catenin staining, as well as tumours with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/β-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5–121.2 months) from diagnosis. All three patients with focal nuclear staining of β-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome, indicating that therapy de-escalation should be considered. International consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.