BACKGROUND & 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 in 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.

OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy / A. Sciarra, S. Schmidt, A. Pellegrinelli, M. Maggioni, D. Dondossola, J. Pasquier, C. Cigala, D. Tosi, N. Halkic, G. Bulfamante, G. Viale, S. Bosari, C. Balabaud, P. Bioulac-Sage, C. Sempoux. - In: LIVER INTERNATIONAL. - ISSN 1478-3223. - (2018 Sep 15). [Epub ahead of print] [10.1111/liv.13964]

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

A. Sciarra
;
A. Pellegrinelli;D. Dondossola;D. Tosi;G. Bulfamante;G. Viale;S. Bosari;
2018-09-15

Abstract

BACKGROUND & 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 in 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.
hepatocellular adenoma; hepatocyte transporters; hepatospecific magnetic resonance imaging; radio-pathological correlation
Settore MED/08 - Anatomia Patologica
Settore MED/36 - Diagnostica per Immagini e Radioterapia
Settore MED/18 - Chirurgia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/592813
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