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Liver Int. 2019 Jan;39(1):158-167. doi: 10.1111/liv.13964. Epub 2018 Oct 8.

OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy.

Author information

1
Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
2
Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
3
Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland.
4
Pathology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
5
Liver Transplant and General Surgery Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
6
Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
7
Unit of Pathology, San Paolo Hospital Medical School, Department of Health Sciences, University of Milan, Milan, Italy.
8
Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland.
9
European Institute of Oncology, University of Milan, Milan, Italy.
10
Pathology Department, Inserm, UMR-1053, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France.

Abstract

BACKGROUND AND AIMS:

Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd-EOB-DTPA-enhanced MRI.

METHODS:

By means of immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3, in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal malignant transformation (HCA-HCC, n = 4). Results were validated on a supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with Gd-EOB-DTPA MR images.

RESULTS:

All FNH showed a preserved expression of hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of malignant transformation) and HCA-HCC were characterized by preserved/increased OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected the profile predicted by their specific OATPB1/B3 tissue expression. The hyperintense vs hypointense HBP signal criterion was able to distinguish all higher risk HCA and HCA-HCC (100% accuracy).

CONCLUSIONS:

OATPB1/B3 and MRP3 IHC and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA according to their risk of malignant transformation.

KEYWORDS:

hepatocellular adenoma; hepatocyte transporters; hepatospecific magnetic resonance imaging; radio-pathological correlation

PMID:
30218633
DOI:
10.1111/liv.13964

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