ArticleBalkan medical journal2026
Significance of LEF1, ROR2, Cyclin D1, and DNA Methylation Profiling in the Molecular Classification and Prognosis Prediction of Pediatric Medulloblastoma.
Article in Balkan medical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Accurate identification of medulloblastoma molecular subgroups is essential, particularly in settings lacking advanced genomic tools. Conventional markers, such as β-catenin, present significant challenges in reliably detecting the WNT-activated subgroup (WNT-AG). Aims: To evaluate the utility of lymphoid enhancer-binding factor 1 (LEF1), Cyclin D1, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) as immunohistochemical (IHC) markers for molecular subgroup classification and to assess their prognostic significance. Study Design: Retrospective cohort study. Methods: IHC analysis was performed using LEF1, Cyclin D1, and ROR2. Two distinct LEF1 staining patterns were identified: nuclear (nLEF1) and punctate (pLEF1). A subset of 29 cases, selected based on predefined criteria, underwent EPIC array Methylation analysis. Findings were correlated with recurrence and survival outcomes. Results: Among the 94 cases, 12.8% were WNT-AG, 54.3% were sonic hedgehog-activated subgroup (SHH-AG), and 33.0% were Groups 3 and 4 (G3/4). nLEF1 demonstrated higher specificity and sensitivity for WNT-AG than β-catenin, identifying it as a more reliable diagnostic marker. High pLEF1 expression was strongly associated with SHH-AG. Cyclin D1 positivity was predominantly observed in WNT-AG. While ROR2 did not identify WNT-AG effectively, its absence in Group 3 cases was notable. Prognostic analysis revealed that LEF1 expression patterns correlated with favorable survival outcomes: total LEF1 (tLEF1) and nLEF1 were associated with improved overall survival, whereas pLEF1 and tLEF1 were linked to better progression-free survival. Conclusion: Nuclear LEF1 (nLEF1) is at least as effective as β-catenin in identifying WNT-AG and may serve as a superior diagnostic marker. Cyclin D1 can be used as a complementary marker in WNT-AG detection. ROR2 negativity may indicate G3 tumors, though further studies are warranted to confirm its prognostic value.
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