Immunohistochemical staining of LEF-1 is a useful marker for distinguishing WNT-activated Medulloblastomas

Objectives: To investigate lymphoid enhancer factor 1 (LEF-1) protein expression in medulloblastomas (MBs) and its correlation with molecular grouping of MBs. Methods: : Expressions of LEF-1 and β-catenin were detected by immunohistochemistry, and molecular grouping was performed based on the NanoString and sequencing techniques for 30 MBs. Results: : By genetic defining, 3 MBs were WNT-activated , 11 were SHH-activated, 3 were in Group 3 and 13 in Group 4 respectively. Nuclear LEF-1 staining was found in 8 MBs using immunohistochemical method. Three out of 8 showed diffuse and strong nuclear LEF-1 staining which were proved to be WNT-activated genetically, while the other 5 MBs with focal staining were SHH-activated genetically. The expression of LEF-1 protein was significantly correlated with genetically defined WNT-activated MBs ( P< 0.0001). We also found focal nuclear β-catenin expression ( less than 1% of tumor cells）in 5 MBs. LEF-1 positivity was significantly correlated nuclear β-catenin expression (p<0.001). Conclusions: : Immunohistochemical staining of LEF-1 can be used as a substitute for β-Catenin, the latter is difficult to recognize for the cytoplasm/membrane staining background. Diffuse nuclear staining of LEF-1 indicates WNT-activated MB.