Preoperative Multifrequency MR Elastography for Stratifying Wnt/β-Catenin Pathway and Microvascular Invasion Phenotypes in Hepatocellular Carcinoma.

Background: The Wnt/β-catenin signaling pathway and microvascular invasion (MVI) are associated with the prognosis of hepatocellular carcinoma (HCC).

Purpose: To evaluate the Wnt/β-catenin pathway and MVI states using preoperative MR elastography (MRE).

Study Type: Prospective.

Population: 210 participants with surgically confirmed HCC (179 men; mean age 59.6 ± 0.8 years) and preoperative MRI/MRE.

Field Strength/sequence: 1.5 T/3 T, single-shot spin-echo MRE, T2-weighted image, diffusion-weighted imaging, DIXON, and contrast-enhanced T1-weighted imaging using fat-suppressed gradient sequence.

Assessment: Imaging features were assessed using major and ancillary features of Liver Imaging Reporting and Data System v2018, together with MRE-derived stiffness and viscosity. Glutamine synthetase, β-catenin, and MVI expression were evaluated in surgical specimens. Recurrence-free survival (RFS) was assessed in participants with available follow-up data.

Statistical Tests: Multivariate logistic regression, Cox proportional hazards regression, receiver operating characteristic analysis, and Kaplan-Meier survival analysis with log-rank test were used. P-value < 0.05 was considered significant.

Results: MVI and Wnt/β-catenin pathway activation were found in 59 and 105 participants, respectively. Wnt/β-catenin pathway activation (hazard ratio [HR] = 0.405, 95% CI: 0.247-0.664) and MVI (HR = 1.737, 95% CI: 1.021-2.954) predicted postoperative recurrence. Elevated tumor stiffness (odds ratio [OR] = 1.582, 95% CI: 1.034-2.420), total bilirubin > 24 μmol/L (OR = 2.465, 95% CI: 1.154-5.267), smooth tumor margins (OR = 2.226, 95% CI: 1.157-4.283), and mosaic architecture (OR = 1.990, 95% CI: 1.029-3.851) were significantly associated with Wnt/β-catenin pathway activation. Decreased tumor stiffness (OR = 2.075, 95% CI: 1.095-3.937), non-smooth margin (OR = 8.246, 95% CI: 3.048-22.307), peritumoral enhancement (OR = 2.677, 95% CI: 1.081-6.630), incomplete or absent capsule enhancement (OR = 3.846, 95% CI: 1.680-8.800), and multiplicity (OR = 2.579, 95% CI: 1.036-6.420) were independent indicators of MVI. MVI-positive HCC with Wnt/β-catenin pathway silence, median RFS was only 6.33 months. Risk factors for this phenotype included decreased tumor stiffness, non-smooth tumor margins, incomplete or absent capsule enhancement, and corona enhancement.

Data Conclusion: Integrating tumor stiffness with morphological features may help preoperatively identifying HCC with poor postoperative outcomes.

Evidence Level: 1.

Technical Efficacy: Stage 2.