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Immunohistochemical and nanoString-Based Subgrouping of Clinical Medulloblastoma Samples

2020; Oxford University Press; Volume: 79; Issue: 4 Linguagem: Inglês

10.1093/jnen/nlaa005

1554-6578

Colleen D’Arcy, Liana Nobre, Anthony Arnaldo, Vijay Ramaswamy, Michael D. Taylor, Lili‐Naz Hazrati, Cynthia Hawkins,

Genomics and Chromatin Dynamics

Abstract The diagnosis of medulloblastoma incorporates the histologic and molecular subclassification of clinical medulloblastoma samples into wingless (WNT)-activated, sonic hedgehog (SHH)-activated, group 3 and group 4 subgroups. Accurate medulloblastoma subclassification has important prognostic and treatment implications. Immunohistochemistry (IHC)-based and nanoString-based subgrouping methodologies have been independently described as options for medulloblastoma subgrouping, however have not previously been directly compared. We describe our experience with nanoString-based subgrouping in a clinical setting and compare this with our IHC-based results. Study materials included FFPE tissue from 160 medulloblastomas. Clinical data and tumor histology were reviewed. Immunohistochemical-based subgrouping using β-catenin, filamin A and p53 antibodies and nanoString-based gene expression profiling were performed. The sensitivity and specificity of IHC-based subgrouping of WNT and SHH-activated medulloblastomas was 91.5% and 99.54%, respectively. Filamin A immunopositivity highly correlated with SHH/WNT-activated subgroups (sensitivity 100%, specificity 92.7%, p < 0.001). Nuclear β-catenin immunopositivity had a sensitivity of 76.2% and specificity of 99.23% for detection of WNT-activated tumors. Approximately 23.8% of WNT cases would have been missed using an IHC-based subgrouping method alone. nanoString could confidently predict medulloblastoma subgroup in 93% of cases and could distinguish group 3/4 subgroups in 96.3% of cases. nanoString-based subgrouping allows for a more prognostically useful classification of clinical medulloblastoma samples.