P03.17 Immunohistochemical sub-grouping of pediatric and adult medulloblastoma: a preliminary study

Medulloblastoma (MB) is the most common malignant childhood brain tumor and may affect young adults. Even if today effective therapies are available, patients often suffer from severe long-term adverse effects, relapses and even secondary tumors. Standard therapy is currently based on post-surgical radiotherapy (RT) and chemotherapy. However, exceptions to this protocol might be used to reduce toxicity affecting brain development and consequent cognitive dysfunctions. A more rational therapeutic strategy may be based on targeting signaling pathways that drive MB growth and dissemination. Recently molecular profiling has identified four molecular subtypes of MB. Groups 1 and 2 (WNT and SHH groups) derive from disregulation of these key developmental signaling pathways and Groups 3 and 4 are associated with up-regulation of c-MYC and n-MYC respectively. This subgroup stratification has generated four genetically distinct tumor identities, each with a characteristic clinical presentation and prognosis. Group 3, associated whit the worst prognosis, was recently characterized by increased CD133 positive Cancer Stem Cells and the activation of STAT signaling pathway. The correct sub-classification in the four molecular groups becomes a key step for risk stratification. The use of an appropriate panel of antibodies may help to subclassify MB patients in these molecular groups and to open the possibility of innovative therapies based on specific inhibitors of the signaling pathways involved. To verify the feasibility of the use of Immunohistochemistry (IHC) for the molecular classification of MD and the possible differences between pediatric and adult MB we retrieved form pathology files 21 adult and 22 pediatric MB. We tested the expression of β-catenin, Filamin A, GAB1, KCNA1, YAP1 and NPR3 and compared the results on adult and pediatric MB. Results were somewhat different in the pediatric (Group 1: 36%, Group 2: 48%, Group 3: 8%, Group 4: 8%) from the adult cases (Group 1: 0%, Group 2: 73%, Group 3: 5,3% Group 4: 21%). This preliminary study demonstrates the usefulness of IHC for the application of the molecular classification of MB. Such IHC approach may represent the base for the development of targeted therapies for MB in pediatric and adult patients with the goal of improving cure rate and hopefully decreasing the side effects of Radiotherapy and Chemotherapy.