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OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd‐EOB‐DTPA uptake and correlates with risk of malignancy
Author(s) -
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,
BioulacSage Paulette,
Sempoux Christine
Publication year - 2019
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13964
Subject(s) - hepatocellular adenoma , malignancy , medicine , hepatocellular carcinoma , adenoma , gastroenterology , oncology
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.