The Role of Immunohistochemistry as a Surrogate for Molecular Subtyping of Medulloblastoma

Background: Immunohistochemistry (IHC) plays a pivotal role in the molecular classification of medulloblastoma (MB), enabling accurate subgrouping in routine pathology. Unlike costly genomic techniques, IHC is accessible, cost-effective, and widely applicable. Its integration into diagnostic workflows significantly enhances clinical decision-making and patient stratification.
Aim: This study aimed to classify MB cases into their molecular subtypes using IHC of YAP1, GAB1, Beta-catenin and P53 then assess the relation between histological and molecular subtypes of MB and clinicopathological data.
Patients and Methods: This retrospective study included 50 patients with MB diagnosed from the period from 2017 to 2023 at Pathology Laboratory at Mansoura Faculty of Medicine. IHC for YAP1, GAB1, β-catenin and P53 was done to classify the cases into the molecular subtypes.
Results: Among the 50 MB, Classic histology was most common (48%), followed by desmoplastic/nodular (26%), and large cell/anaplastic (22%). Molecular subtyping revealed 58% non-WNT/non-SHH, 30% SHH-activated, and 12% WNT-activated tumors. Significant associations were observed between molecular and histological subtypes and key clinical parameters including age, location, size, metastasis, and risk stratification.
Conclusion: This study demonstrates that immunohistochemistry serves as a reliable and feasible alternative for molecular subtyping of MB, particularly in settings where advanced molecular diagnostics are not available. The observed associations between molecular subgroups, histological variants, and clinical features underscore the importance of combining histopathological evaluation with immunohistochemical analysis to enhance diagnostic precision and support personalized risk-based management strategies.