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Updated: Mar 11, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
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AXIN1 Mutated Hepatocellular Carcinoma.

Michael Torbenson1, Chantal E McCabe2, Jessica D Hohenstein2

  • 1Division of Laboratory Medicine and Anatomic Pathology.

The American Journal of Surgical Pathology
|March 10, 2026
PubMed
Summary
This summary is machine-generated.

Hepatocellular carcinomas with AXIN1 mutations show classic Wnt pathway activation morphology, but with lower Wnt pathway activation levels compared to CTNNB1 mutations. Tumor progression can alter Wnt activation levels.

Keywords:
APCAXIN1CTNNB1beta cateninglutamine synthetasehepatocellular carcinoma

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hepatocellular carcinoma (HCC) harbors mutations in Wnt pathway genes, notably CTNNB1, which dictates tumor morphology and pathway activation.
  • AXIN1 is crucial for Wnt pathway regulation, yet its role in HCC morphology and Wnt activation remains less understood.

Purpose of the Study:

  • To investigate the morphological characteristics and Wnt pathway activation status of AXIN1-mutated hepatocellular carcinomas.
  • To compare these features with tumors mutated in CTNNB1, APC, and other Wnt pathway genes.

Main Methods:

  • Histological examination of 18 AXIN1-mutated HCCs and control groups (CTNNB1, APC, Other Wnt genes).
  • Immunohistochemistry for beta-catenin and glutamine synthetase to assess Wnt pathway activation.
  • Gene expression analysis using TCGA data for supplementary findings.

Main Results:

  • Classic Wnt pathway-associated morphology was observed in AXIN1-mutated HCCs (44%), similar to CTNNB1 (59%), APC (67%), and Other (20%) groups.
  • Wnt pathway activation was detected in 61% of AXIN1-mutated HCCs, albeit at lower levels than CTNNB1-mutated tumors (88%).
  • Glutamine synthetase staining revealed a novel 'progressed pattern,' and Wnt activation levels can change during tumor progression.

Conclusions:

  • Mutations in AXIN1, APC, and other Wnt pathway genes can lead to the characteristic morphology seen in CTNNB1-mutated HCC.
  • AXIN1-mutated HCCs exhibit detectable Wnt pathway activation, though it is less pronounced than in CTNNB1-mutated tumors.
  • Tumor progression influences Wnt pathway activation levels in hepatocellular carcinoma.