Abstract
BackgroundMedulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. This study aimed to validate MB molecular subgrouping using surrogate immunohistochemistry and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) and progression-free survival (PFS) of MB patients. This study included 40 MBs; immunohistochemical staining, using β-catenin and GRB2-Associated Binding Protein 1 (GAB1) antibodies, was used to classify MB cases into wingless signaling activated (WNT), sonic hedgehog (SHH), and non-WNT/SHH molecular subgroups. Nuclear morphometric analysis (for assessment of degree of anaplasia) and Kaplan-Meier survival curves were done.ResultsMB cases were classified into WNT (10%), SHH (30%), and non-WNT/SHH (60%) subgroups. Histopathological types differed significantly according to tumor location (p< 0.001), degree of anaplasia (p = 0.014), molecular subgroups (p < 0.001), and risk stratification (p = 0.008). Molecular subgroups differed significantly in age distribution (p = 0.031), tumor location (p< 0.001), histopathological variants (p < 0.001), and risk stratification (p < 0.001). OS was 77.5% and 50% after 1 and 2 years, while PFS was 65% and 27.5% after 1 and 2 years, respectively. OS and PFS were associated significantly with histopathological variants (p < 0.001 and 0.001), molecular subgroups (p = 0.012 and 0.005), and risk stratification (p < 0.001 and < 0.001), respectively.ConclusionsMedulloblastoma classification based on molecular subgroups, together with clinicopathological indicators, mainly histopathological types; accurately risk stratifies MB patients and predicts their survival.
Highlights
Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups
Cases were of adequate formalin-fixed paraffinembedded (FFPE) tissue blocks, complete clinical data including age at diagnosis, sex, tumor location, computerized tomography (CT) mass size, metastasis at diagnosis (M0 or M+), type of surgery, size of residual mass after surgery, received postoperative radiation and/or chemotherapy, and complete follow-up data
Histopathological features, nuclear morphometric analysis for degree of anaplasia, and molecular subgroups Based on microscopic evaluation of 40 MBs, 16 cases (40%) were of large cell/anaplastic (LCA) histology, 14 cases of classic histology (35%), and 10 cases were D/N MB (25%)
Summary
Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. Advances in genome-wide analysis and gene transcription revealed that medulloblastomas are heterogeneous tumors, consisting of distinct molecular subgroups; each has a unique genomic profile [wingless signaling activated (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH that further includes group 3 and group 4 medulloblastomas]. This molecular classification suggests different cellular origins with variable driving mutations [1]. Few studies used more simple techniques as fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC), as surrogate methods for molecular subgrouping Such techniques are applicable and provide reliable results on routinely processed formalin-fixed paraffinembedded (FFPE) specimens [1]
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