Significance of LEF1, ROR2, Cyclin D1, and DNA Methylation Profiling in the Molecular Classification and Prognosis Prediction of Pediatric Medulloblastoma

Background: Accurate identification of medulloblastoma molecular 4 (G3/4). nLEF1 demonstrated higher specificity and sensitivity for WNT-subgroups is essential, particularly in settings lacking advanced genomic AG than β-catenin, identifying it as a more reliable diagnostic marker. tools. Conventional markers, such as β-catenin, present significant High pLEF1 expression was strongly associated with SHH-AG. Cyclin D1 challenges in reliably detecting the WNT-activated subgroup (WNT-AG). positivity was predominantly observed in WNT-AG. While ROR2 did not Aims: To evaluate the utility of lymphoid enhancer-binding factor ₁ identify WNT-AG effectively, its absence in Group 3 cases was notable. (LEF1), Cyclin _{D1, and receptor} tyrosine _{kinase-like orphan receptor 2} Prognostic analysis revealed that LEF1 expression patterns correlated (ROR2) as immunohistochemical (IHC) markers for molecular subgroup ^with favorable survival outcomes: total LEF1 (tLEF1) and nLEF1 were classification and to assess their prognostic significance. associated with improved overall survival, whereas pLEF1 and tLEF1 were Study Design: Retrospective cohort study. linked to better progression-free survival. Methods: IHC analysis was performed using LEF1, Cyclin _{D1, and ROR2.} Conclusion: Nuclear LEF1 (nLEF1) is at least as effective as β-catenin in Two distinct LEF1 staining patterns were identified: nuclear (nLEF1) and ^identifying WNT-AG ^{and may} serve as a superior diagnostic marker. Cyclin punctate (pLEF1). A subset of 29 cases, selected based on predefined ^{D1 can be used as} a complementary marker in WNT-AG detection. ROR2 criteria, underwent _{EPIC array Methylation} analysis. Findings _were negativity may indicate G3 tumors, though further studies are warranted correlated with recurrence and survival outcomes. to confirm its prognostic value. 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