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Updated: Nov 25, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Diagnostic Accuracy of a Reduced Immunohistochemical Panel in Medulloblastoma Molecular Subtyping, Correlated to
Arnault Tauziède-Espariat1, Sophie Huybrechts2, Emilie Indersie3,4
1Departments of Neuropathology.
Abstract:
Medulloblastomas (MBs) are the most frequent childhood malignant brain tumor. Four histopathologic variants and 4 genetic subgroups have been defined in the World Health Organization (WHO) 2016 Classification and constitute major risk stratification items directly affecting the patient management. Although MB subgroups have been molecularly defined, immunohistochemical surrogates are needed. The aim of our retrospective study was to evaluate the concordance between immunohistochemistry, using 4 antibodies (YAP1, GAB1, OTX2, and β-catenin), and DNA-methylation profiling in MB subgrouping. From a series of 155 MBs, the κ coefficient of concordance was almost perfect (0.90), with only 8/152 discrepant cases (no DNA-methylation analysis was available in 3 cases). Interestingly, the discrepancies mostly concerned (7/8 cases) MBs with divergent differentiations (myogenic, melanotic, and others) with all of those classified into group 3 (n=6) and group 4 (n=1) by DNA-methylation profiling. Another discrepant case concerned a WNT-activated MB (showing only 1% of immunopositive tumor cell nuclei), highlighting the difficulties of determining an appropriate β-catenin immunostaining cutoff. The high concordance of the routine immunohistochemical panel (YAP1, GAB1, OTX2, and β-catenin) and DNA-methylation profiling confirm its utility as a reliable predictive marker of molecular subtype in MBs. We analyzed the accuracy of 10 different IHC combinations for the determination of MB subtype and found that a combination of 2 antibodies (YAP1 and OTX2) allows for the successful characterization of 144 cases of 152 cases. Finally, our series extends the molecular data of the rare morphologic variant of MBs with melanotic/myogenic differentiations.
Insights
Immunohistochemistry (IHC) reliably predicts medulloblastoma (MB) molecular subgroups, aiding childhood brain tumor management. A panel including YAP1 and OTX2 accurately identifies MB subtypes, simplifying diagnosis.
Area of Science:
- Pediatric neuro-oncology
- Molecular pathology
- Cancer diagnostics
Background:
- Medulloblastomas (MBs) are the most common malignant pediatric brain tumors.
- Accurate molecular subtyping is crucial for risk stratification and patient management.
- Current molecular subtyping requires complex DNA-methylation profiling; immunohistochemical (IHC) surrogates are needed.
Purpose of the Study:
- To assess the concordance between IHC markers and DNA-methylation profiling for MB subgrouping.
- To identify an efficient IHC panel for routine MB molecular subtyping.
Main Methods:
- Retrospective analysis of 155 medulloblastoma cases.
- Immunohistochemistry was performed using YAP1, GAB1, OTX2, and β-catenin antibodies.
- Results were compared with DNA-methylation profiling data.
Main Results:
- A high concordance (κ=0.90) was observed between IHC and DNA-methylation profiling.
- A combination of YAP1 and OTX2 antibodies accurately characterized 144 out of 152 MB cases.
- Discrepancies were noted in rare divergent differentiation MBs and WNT-activated MBs, highlighting IHC cutoff challenges.
Conclusions:
- The routine IHC panel (YAP1, GAB1, OTX2, β-catenin) is a reliable surrogate for MB molecular subtyping.
- A simplified panel of YAP1 and OTX2 shows high accuracy for MB subgroup determination.
- This study provides molecular data for rare MB variants and supports IHC's role in clinical diagnostics.
