808 Analysis of Medulloblastomas Subgroups in Pediatric Patients in Latin-America

Abstract

INTRODUCTION: The 4 groups molecular-based classification of medulloblastomas is widely accepted. However, technology inaccessibility and low-quality formalin-fixed and paraffin-embedded (FFPE) samples, unable its application for most Latin-American cancer centers. METHODS: The goal of this study was to perform a feasibility analysis based on 18 mRNA expression by qPCR integrated with immunohistochemistry (IH) and fluorescent hybridization in situ (FISH) (c-MYC, n-MYC and monosomy 6) for molecular stratification to create an International Treatment Protocol at a low cost for low-income centers. RESULTS: Fifty-four FFPE samples were classified according to histologic and molecular aspects. Classic medulloblastoma was the commonest histology (53.7%), followed by desmoplastic/extensive nodularity (24.1%), NOS (16,7%) and anaplastic (5,6%). IH markers classified patients in three groups (WNT, SHH and non-WNT/non-SHH) in 98% of cases. PCR-based method confirmed results from IH in 81.5%. Additionally, it detected WNT activation in 2 more patients, previously classified as SHH. For both cases, the presence of monosomy 6 confirmed WNT subgroup. The integration of these three techniques resulted in the following frequencies: WNT (13.0%), SHH (38.9%), group 3 (9.3%), group 4 (20.3%) and non-WNT/non-SHH (18.5%). From 40 patients with clinical follow-up available, 3-year overall survival (n = 40) for low, intermediate and high-risk groups were 100%, 60% and 20%, respectively (p < 0.05), based only in molecular criteria, which confirmed the prognostic importance of this method at a low cost. CONCLUSIONS: The prognosis of the treatment of medulloblastomas has changed after novel studies on the molecular subgroups and the introduction of target-based therapy. The current protocol will enable different centers to implement treatment based on the knowledge of molecular subgroups.