Characterization of high- and low-risk hepatocellular adenomas by magnetic resonance in an animal model of glycogen storage disease type 1A

Author:

Resaz Roberta1,Rosa Francesca23ORCID,Grillo Federica45,Basso Luca23ORCID,Segalerba Daniela1,Puglisi Andrea1ORCID,Bosco Maria Carla1,Mastracci Luca45,Neumaier Carlo E.3,Varesio Luigi1,Eva Alessandra1ORCID

Affiliation:

1. Laboratory of Molecular Biology, Istituto Giannina Gaslini, Genova, Italy

2. Department of Science of Health (DISSAL), University of Genova, Genova, Italy

3. Department of Radiology, Ospedale Policlinico San Martino, Genova, Italy

4. Pathology Unit, Department of Surgical Sciences and Integrates Diagnostics (DISC), University of Genova, Genova, Italy

5. Ospedale Policlinico San Martino, Genova, Italy

Abstract

Purpose: Hepatocellular adenomas (HCA) are benign tumors whose most serious complications are hemorrhage and malignant transformation to hepatocellular carcinoma (HCC). Among various subtypes of HCA, β-catenin-activated (bHCA) are at greater risk of malignant transformation. Magnetic Resonance Imaging (MRI) is an important tool to differentiate benign and malignant hepatic lesions, and preclinical experimental approaches may help develop a method to identify MRI features associated with bHCA. HCA are associated to various pathologies, including Glycogen Storage Disease 1a (GSD1a). We have utilized a mouse model for GSD1a that develops HCA and HCC and analyzed these mice in order to distinguish low-risk from high-risk tumors. Methods: Animals were scanned by MRI using a hepato-specific contrast agent. Mice were sacrificed after MRI and lesions were classified using immunohistochemistry. Results: 45% of the animals developed focal lesions. MRI identified 4 different patterns after contrast administration: isointense, hyperintense, hypointense lesions and lesions with a peripheral contrast enhancement. After contrast administration, only bHCA and HCC were hypointense on T1-WI and mildly hyperintense T2-WI. Conclusions: We show that high-risk adenomas display MRI features clearly distinguishable from those exhibited by low-risk adenomas, indicating that MRI is a reliable method for early diagnosis and classification of HCA, necessary for correct patient management.

Funder

Associazione Italiana per la Ricerca sul Cancro

Compagnia di San Paolo

Associazione Italiana Glicogenosi

Ministero della Salute

Publisher

The Company of Biologists

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology and Microbiology (miscellaneous),Medicine (miscellaneous),Neuroscience (miscellaneous)

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