Can MRI features predict clinically relevant hepatocellular carcinoma genetic subtypes?

Abstract

Purpose: Recent studies in cancer genomics have revealed core drivers for hepatocellular carcinoma (HCC) pathogenesis. We aim to study whether MRI features can serve as non-invasive markers for the prediction of common genetic subtypes of HCC.

Methods: Sequencing of 447 cancer-implicated genes was performed on 43 pathology proven HCC from 42 patients, who underwent contrast-enhanced MRI followed by biopsy or resection. MRI features were retrospectively evaluated including tumor size, infiltrative tumor margin, diffusion restriction, arterial phase hyperenhancement, non-peripheral washout, enhancing capsule, peritumoral enhancement, tumor in vein, fat in mass, blood products in mass, cirrhosis and tumor heterogeneity. Fisher's exact test was used to correlate genetic subtypes with imaging features. Prediction performance using correlated MRI features for genetic subtype and inter-reader agreement were assessed.

Results: The two most prevalent genetic mutations were TP53 (13/43, 30%) and CTNNB1 (17/43, 40%). Tumors with TP53 mutation more often demonstrated an infiltrative tumor margin on MRI (p = 0.01); inter-reader agreement was almost perfect (kappa = 0.95). The CTNNB1 mutation was associated with peritumoral enhancement on MRI (p = 0.04), inter-reader agreement was substantial (kappa = 0.74). The MRI feature of an infiltrative tumor margin correlated with the TP53 mutation with accuracy, sensitivity, and specificity of 74.4%, 61.5% and 80.0%, respectively. Peritumoral enhancement correlated with the CTNNB1 mutation with accuracy, sensitivity, and specificity of 69.8%, 47.0% and 84.6%, respectively.

Conclusion: An infiltrative tumor margin on MRI correlated with TP53 mutation and peritumoral enhancement correlated with CTNNB1 mutation in HCC. Absence of these MRI features are potential negative predictors of the respective HCC genetic subtypes that have implications for prognosis and treatment response.

Keywords: Carcinoma, hepatocellular; Liver; Magnetic resonance imaging; Mutation.