Optimizing Immunohistochemical Surrogate Panels for 1p/19q Codeletion in IDH-Mutant Adult Diffuse Gliomas: Diagnostic Performance of Vimentin and H3K27me3

Background: Differentiating IDH-mutant astrocytomas from IDH-mutant, 1p/19q-codeleted oligodendrogliomas can be challenging due to overlapping histology, particularly in small samples. We evaluated whether quantitative expression of vimentin and H3K27me3 can serve as reliable surrogate markers for 1p/19q-codeletion status. Methods: A cohort of 71 adult IDH-mutant diffuse gliomas (34 astrocytomas, 37 oligodendrogliomas) was analyzed. Marker expressions were evaluated together with key histopathological features. Results: Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, multivariable logistic regression, and hierarchical modeling. Both H3K27me3 positivity (≥30% cut-off; 96.97% sensitivity, 88.89% specificity) and vimentin positive area (≥40% cut-off; 100% sensitivity, 89.19% specificity) were significantly higher in astrocytomas than in oligodendrogliomas (p < 0.0001). Classical oligodendroglial features correlated with lower expression of both markers, whereas gemistocytes correlated with higher expression. Individual AUCs were high for ATRX (0.933), H3K27me3 (0.928), and vimentin (0.944). In multivariable regression containing both markers, vimentin proved to be the dominant predictor (p = 0.008), rendering H3K27me3 redundant (p = 0.725). Hierarchical regression showed that adding vimentin or H3K27me3 to ATRX individually significantly improved performance (AUC = 0.994, p < 0.001). However, adding H3K27me3 to the ATRX + vimentin combination provided no significant improvement (p = 0.063). Conclusions: Vimentin loss and H3K27me3 loss are effective individual surrogate markers for 1p/19q-codeletion in adult IDH-mutant diffuse gliomas. However, multivariable and hierarchical regression modeling demonstrates that vimentin is the dominant predictor that renders H3K27me3 statistically redundant. A streamlined two-marker immunohistochemical panel combining ATRX and vimentin provides optimal diagnostic accuracy (AUC = 0.994) without requiring additional H3K27me3 testing, offering an accessible workflow for routine neuropathology.