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

Amedeo Sciarra, Sabine Schmidt, Alessandro Pellegrinelli, Marco Maggioni, Daniele Dondossola, Jerome Pasquier, Claudia Cigala, Delfina Tosi, Nermin Halkic, Gaetano Bulfamante, Giuseppe Viale, Silvano Bosari, Charles Balabaud, Paulette Bioulac-Sage, Christine Sempoux

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)158-167
Number of pages10
JournalLiver International
Volume39
Issue number1
DOIs
Publication statusPublished - Jan 2019

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Liver Cell Adenoma
Focal Nodular Hyperplasia
Neoplasms
Magnetic Resonance Imaging
gadolinium ethoxybenzyl DTPA
Hepatocytes
Immunohistochemistry

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OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy. / Sciarra, Amedeo; Schmidt, Sabine; Pellegrinelli, Alessandro; Maggioni, Marco; Dondossola, Daniele; Pasquier, Jerome; Cigala, Claudia; Tosi, Delfina; Halkic, Nermin; Bulfamante, Gaetano; Viale, Giuseppe; Bosari, Silvano; Balabaud, Charles; Bioulac-Sage, Paulette; Sempoux, Christine.

In: Liver International, Vol. 39, No. 1, 01.2019, p. 158-167.

Research output: Contribution to journalArticle

Sciarra, A, Schmidt, S, Pellegrinelli, A, Maggioni, M, Dondossola, D, Pasquier, J, Cigala, C, Tosi, D, Halkic, N, Bulfamante, G, Viale, G, Bosari, S, Balabaud, C, Bioulac-Sage, P & Sempoux, C 2019, 'OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy', Liver International, vol. 39, no. 1, pp. 158-167. https://doi.org/10.1111/liv.13964
Sciarra, Amedeo ; Schmidt, Sabine ; Pellegrinelli, Alessandro ; Maggioni, Marco ; Dondossola, Daniele ; Pasquier, Jerome ; Cigala, Claudia ; Tosi, Delfina ; Halkic, Nermin ; Bulfamante, Gaetano ; Viale, Giuseppe ; Bosari, Silvano ; Balabaud, Charles ; Bioulac-Sage, Paulette ; Sempoux, Christine. / OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy. In: Liver International. 2019 ; Vol. 39, No. 1. pp. 158-167.
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title = "OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy",
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.",
author = "Amedeo Sciarra and Sabine Schmidt and Alessandro Pellegrinelli and Marco Maggioni and Daniele Dondossola and Jerome Pasquier and Claudia Cigala and Delfina Tosi and Nermin Halkic and Gaetano Bulfamante and Giuseppe Viale and Silvano Bosari and Charles Balabaud and Paulette Bioulac-Sage and Christine Sempoux",
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T1 - OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy

AU - Sciarra, Amedeo

AU - Schmidt, Sabine

AU - Pellegrinelli, Alessandro

AU - Maggioni, Marco

AU - Dondossola, Daniele

AU - Pasquier, Jerome

AU - Cigala, Claudia

AU - Tosi, Delfina

AU - Halkic, Nermin

AU - Bulfamante, Gaetano

AU - Viale, Giuseppe

AU - Bosari, Silvano

AU - Balabaud, Charles

AU - Bioulac-Sage, Paulette

AU - Sempoux, Christine

N1 - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

U2 - 10.1111/liv.13964

DO - 10.1111/liv.13964

M3 - Article

C2 - 30218633

VL - 39

SP - 158

EP - 167

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 1

ER -