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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Diagnostic utility of LEF1 and β-catenin in WNT pathway tumors with CTNNB1 mutation.

Can Li1, Lingdan Dong2, Li Zhu1

  • 1Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

World Journal of Surgical Oncology
|January 29, 2025
PubMed
Summary

Lymphoid enhancer factor 1 (LEF1) combined with β-catenin improves diagnosis of WNT/β-catenin pathway tumors, including basal cell adenoma and pancreatic solid pseudopapillary neoplasm. This combination offers enhanced accuracy for identifying these specific tumor types.

Keywords:
CTNNB1 gene mutationImmunohistochemical markerLEF1WNT signaling pathway tumorsΒ-catenin

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • The WNT/β-catenin signaling pathway is crucial in various neoplasms.
  • CTNNB1 gene mutations, particularly in exon 3, activate this pathway.
  • β-catenin is a known marker, but its diagnostic utility can be limited by variable expression.

Purpose of the Study:

  • To compare the diagnostic utility of lymphoid enhancer factor 1 (LEF1) and β-catenin.
  • To evaluate LEF1 and β-catenin as biomarkers in basal cell adenoma (BA), desmoid-type fibromatosis (DF), and pancreatic solid pseudopapillary neoplasm (SPN).
  • To assess the combined diagnostic value of LEF1 and β-catenin in WNT/β-catenin pathway tumors with CTNNB1 exon 3 mutations.

Main Methods:

  • Immunohistochemical analysis of LEF1 and β-catenin expression in 80 tumor samples (26 BA, 30 DF, 24 SPN).
  • Positive staining defined as nuclear expression in >50% of tumor cells.
  • Comparison of diagnostic rates for LEF1 alone, β-catenin alone, and their combination.

Main Results:

  • LEF1 alone increased diagnostic rates for BA (46.16%) and SPN (16.67%) compared to β-catenin alone.
  • Combined LEF1 and β-catenin significantly improved diagnostic ratios for BA (46.16%), SPN (16.67%), and overall (21.25%).
  • While LEF1 and β-catenin alone showed no significant difference, their combined use was highly significant (P=0.001) for WNT pathway tumors.

Conclusions:

  • LEF1 serves as a valuable complementary marker to β-catenin for diagnosing WNT/β-catenin pathway tumors.
  • The combined application of LEF1 and β-catenin enhances diagnostic accuracy for BA, DF, and SPN.
  • This dual marker approach aids in the identification of WNT pathway tumors driven by CTNNB1 exon 3 mutations.