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

Diagn Pathol. 2022 Sep 13;17(1):69. doi: 10.1186/s13000-022-01250-3.

Abstract

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 supplement for β-catenin to diagnosis WNT-activated Medulloblastomas, when β-catenin is difficult to recognize for its cytoplasm/membrane staining background. Diffuse nuclear staining of LEF-1 indicates WNT-activated MB.

Keywords: Immunohistochemistry; LEF-1; Medulloblastoma; WNT-activated; β-catenin.

MeSH terms

  • Biomarkers
  • Cerebellar Neoplasms* / diagnosis
  • Humans
  • Medulloblastoma* / diagnosis
  • Medulloblastoma* / genetics
  • Medulloblastoma* / metabolism
  • Staining and Labeling
  • TCF Transcription Factors
  • beta Catenin / metabolism

Substances

  • Biomarkers
  • TCF Transcription Factors
  • beta Catenin