Skip to main content
Top
Published in: Japanese Journal of Radiology 6/2012

01-07-2012 | Original Article

Hepatocyte transporter expression in FNH and FNH-like nodule: correlation with signal intensity on gadoxetic acid enhanced magnetic resonance images

Authors: Norihide Yoneda, Osamu Matsui, Azusa Kitao, Ryuuichi Kita, Kazuto Kozaka, Wataru Koda, Satoshi Kobayashi, Toshifumi Gabata, Hiroko Ikeda, Yasunori Sato, Yasuni Nakanuma

Published in: Japanese Journal of Radiology | Issue 6/2012

Login to get access

Abstract

Purpose

Our aim was to evaluate the hepatocyte transporters in focal nodular hyperplasia (FNH) and FNH-like lesions and to correlate the grade of its expression with signal intensity on the hepatobiliary phase (HB phase) of gadoxetic-acid-enhanced magnetic resonance imaging (EOB-MRI).

Materials and methods

Thirteen histopathological confirmed cases including eight with EOB-MRI were studied. Immunohistochemical staining for transporter was performed and its grade semiquantitatively analyzed.

Results

Histopathologically, ten cases showed almost equal organic anion transporter polypeptide (OATP) 8 expression relative to the surrounding liver; the remaining three showed stronger OATP8 expression. In eight cases with EOB-MRI, two demonstrated more hyperintensity on the HB phase, and their OATP8 expression was stronger compared with the surrounding liver. The remaining six cases showed isointensity on the HB phase and revealed almost equal OATP8 expression. The expression of export transporter multi-drug-resistant proteins (MRP) 1 and 2 were almost equal relative to the surrounding liver in most cases (11/12, 92 %; 11/12, 92 %, respectively), whereas MRP3 focally overexpressed in 75 % (9/12) of cases.

Conclusion

FNH and FNH-like nodules revealed equal or stronger OATP8 expression than background liver. OATP8 expression showed significant correlation with signal intensity on the HB phase.
Literature
1.
go back to reference Vogl T, Kümmel S, Hammerstingl R, Schellenbeck M, Schumacher G, Balzer T, et al. Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology. 1996;200(1):59–67.PubMed Vogl T, Kümmel S, Hammerstingl R, Schellenbeck M, Schumacher G, Balzer T, et al. Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology. 1996;200(1):59–67.PubMed
2.
go back to reference Bluemke D, Sahani D, Amendola M, Balzer T, Breuer J, Brown JJ, et al. Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study. Radiology. 2005;237(1):89–98.PubMedCrossRef Bluemke D, Sahani D, Amendola M, Balzer T, Breuer J, Brown JJ, et al. Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study. Radiology. 2005;237(1):89–98.PubMedCrossRef
3.
go back to reference Reimer P, Schneider G, Schima W. Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications. Eur Radiol. 2004;14(4):559–78.PubMedCrossRef Reimer P, Schneider G, Schima W. Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications. Eur Radiol. 2004;14(4):559–78.PubMedCrossRef
4.
go back to reference Schuhmann-Giampieri G, Schmitt-Willich H, Press W, Negishi C, Weinmann H, Speck U. Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology. 1992;183(1):59–64.PubMed Schuhmann-Giampieri G, Schmitt-Willich H, Press W, Negishi C, Weinmann H, Speck U. Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology. 1992;183(1):59–64.PubMed
5.
go back to reference Huppertz A, Haraida S, Kraus A, Zech CJ, Scheidler J, Breuer J, et al. Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT—initial observations. Radiology. 2005;234(2):468–78.PubMedCrossRef Huppertz A, Haraida S, Kraus A, Zech CJ, Scheidler J, Breuer J, et al. Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT—initial observations. Radiology. 2005;234(2):468–78.PubMedCrossRef
6.
go back to reference Hamm B, Staks T, Mühler A, Bollow M, Taupitz M, Frenzel T, et al. Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology. 1995;195(3):785–92.PubMed Hamm B, Staks T, Mühler A, Bollow M, Taupitz M, Frenzel T, et al. Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology. 1995;195(3):785–92.PubMed
7.
go back to reference Reimer P, Rummeny E, Shamsi K, Balzer T, Daldrup HE, Tombach B, et al. Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. Radiology. 1996;199(1):177–83.PubMed Reimer P, Rummeny E, Shamsi K, Balzer T, Daldrup HE, Tombach B, et al. Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. Radiology. 1996;199(1):177–83.PubMed
8.
go back to reference Zech C, Grazioli L, Breuer J, Reiser M, Schoenberg S. Diagnostic performance and description of morphological features of focal nodular hyperplasia in Gd-EOB-DTPA-enhanced liver magnetic resonance imaging: results of a multicenter trial. Invest Radiol. 2008;43(7):504–11.PubMedCrossRef Zech C, Grazioli L, Breuer J, Reiser M, Schoenberg S. Diagnostic performance and description of morphological features of focal nodular hyperplasia in Gd-EOB-DTPA-enhanced liver magnetic resonance imaging: results of a multicenter trial. Invest Radiol. 2008;43(7):504–11.PubMedCrossRef
9.
go back to reference Vander Borght S, Libbrecht L, Blokzijl H, Faber KN, Moshage H, Aerts R, et al. Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver. J Pathol. 2005;207(4):471–82.PubMedCrossRef Vander Borght S, Libbrecht L, Blokzijl H, Faber KN, Moshage H, Aerts R, et al. Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver. J Pathol. 2005;207(4):471–82.PubMedCrossRef
10.
11.
go back to reference Terminology of Nodular Hepatocellular Lesions. International working party. Hepatology. 1995;22(3):983–93. Terminology of Nodular Hepatocellular Lesions. International working party. Hepatology. 1995;22(3):983–93.
12.
go back to reference Bioulac-Sage P, Balabaud C, Bedossa P, Scoazec JY, Chiche L, Dhillon AP, et al. Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia: Bordeaux update. J Hepatol. 2007;46(3):521–7.PubMedCrossRef Bioulac-Sage P, Balabaud C, Bedossa P, Scoazec JY, Chiche L, Dhillon AP, et al. Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia: Bordeaux update. J Hepatol. 2007;46(3):521–7.PubMedCrossRef
13.
go back to reference Sugihara S, Nakashima O, Kiyomatsu K, Ijiri M, Edamitsu O, Kojiro M. A case of liver cirrhosis with a hyperplastic nodular lesion. Acta Pathol Jpn. 1990;40(9):699–703.PubMed Sugihara S, Nakashima O, Kiyomatsu K, Ijiri M, Edamitsu O, Kojiro M. A case of liver cirrhosis with a hyperplastic nodular lesion. Acta Pathol Jpn. 1990;40(9):699–703.PubMed
14.
go back to reference Terada T, Kitani S, Ueda K, Nakanuma Y, Kitagawa K, Masuda S. Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease. Virchows Arch A Pathol Anat Histopathol. 1993;422(3):247–52.PubMedCrossRef Terada T, Kitani S, Ueda K, Nakanuma Y, Kitagawa K, Masuda S. Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease. Virchows Arch A Pathol Anat Histopathol. 1993;422(3):247–52.PubMedCrossRef
15.
go back to reference Quaglia A, Tibballs J, Grasso A, Prasad N, Nozza P, Davies SE, et al. Focal nodular hyperplasia-like areas in cirrhosis. Histopathology. 2003;42(1):14–21.PubMedCrossRef Quaglia A, Tibballs J, Grasso A, Prasad N, Nozza P, Davies SE, et al. Focal nodular hyperplasia-like areas in cirrhosis. Histopathology. 2003;42(1):14–21.PubMedCrossRef
16.
go back to reference An H, Illei P, Diflo T, John D, Morgan G, Teperman L, et al. Scirrhous changes in dysplastic nodules do not indicate high-grade status. J Gastroenterol Hepatol. 2003;18(6):660–5.PubMedCrossRef An H, Illei P, Diflo T, John D, Morgan G, Teperman L, et al. Scirrhous changes in dysplastic nodules do not indicate high-grade status. J Gastroenterol Hepatol. 2003;18(6):660–5.PubMedCrossRef
17.
go back to reference Nakashima O, Kurogi M, Yamaguchi R, Miyaaki H, Fujimoto M, Yano H, et al. Unique hypervascular nodules in alcoholic liver cirrhosis: identical to focal nodular hyperplasia-like nodules? J Hepatol. 2004;41(6):992–8.PubMedCrossRef Nakashima O, Kurogi M, Yamaguchi R, Miyaaki H, Fujimoto M, Yano H, et al. Unique hypervascular nodules in alcoholic liver cirrhosis: identical to focal nodular hyperplasia-like nodules? J Hepatol. 2004;41(6):992–8.PubMedCrossRef
18.
go back to reference Wanless I, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology. 1985;5(6):1194–200.PubMedCrossRef Wanless I, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology. 1985;5(6):1194–200.PubMedCrossRef
19.
go back to reference Bioulac-Sage P, Balabaud C, Wanless I. Diagnosis of focal nodular hyperplasia: not so easy. Am J Surg Pathol. 2001;25(10):1322–5.PubMedCrossRef Bioulac-Sage P, Balabaud C, Wanless I. Diagnosis of focal nodular hyperplasia: not so easy. Am J Surg Pathol. 2001;25(10):1322–5.PubMedCrossRef
20.
go back to reference Welch T, Sheedy PF 2nd, Johnson C, Stephens DH, Charboneau JW, Brown ML, et al. Focal nodular hyperplasia and hepatic adenoma: comparison of angiography, CT, US, and scintigraphy. Radiology. 1985;156(3):593–5.PubMed Welch T, Sheedy PF 2nd, Johnson C, Stephens DH, Charboneau JW, Brown ML, et al. Focal nodular hyperplasia and hepatic adenoma: comparison of angiography, CT, US, and scintigraphy. Radiology. 1985;156(3):593–5.PubMed
21.
go back to reference Carlson S, Johnson C, Bender C, Welch T. CT of focal nodular hyperplasia of the liver. AJR Am J Roentgenol. 2000;174(3):705–12.PubMed Carlson S, Johnson C, Bender C, Welch T. CT of focal nodular hyperplasia of the liver. AJR Am J Roentgenol. 2000;174(3):705–12.PubMed
22.
go back to reference Brancatelli G, Federle M, Grazioli L, Blachar A, Peterson M, Thaete L. Focal nodular hyperplasia: CT findings with emphasis on multiphasic helical CT in 78 patients. Radiology. 2001;219(1):61–8.PubMed Brancatelli G, Federle M, Grazioli L, Blachar A, Peterson M, Thaete L. Focal nodular hyperplasia: CT findings with emphasis on multiphasic helical CT in 78 patients. Radiology. 2001;219(1):61–8.PubMed
23.
go back to reference Miyayama S, Matsui O, Ueda K, Kifune K, Yamashiro M, Yamamoto T, et al. Hemodynamics of small hepatic focal nodular hyperplasia: evaluation with single-level dynamic CT during hepatic arteriography. AJR Am J Roentgenol. 2000;174(6):1567–9.PubMed Miyayama S, Matsui O, Ueda K, Kifune K, Yamashiro M, Yamamoto T, et al. Hemodynamics of small hepatic focal nodular hyperplasia: evaluation with single-level dynamic CT during hepatic arteriography. AJR Am J Roentgenol. 2000;174(6):1567–9.PubMed
24.
go back to reference Giovanoli O, Heim M, Terracciano L, Bongartz G, Ledermann HP. MRI of hepatic adenomatosis: initial observations with gadoxetic acid contrast agent in three patients. AJR Am J Roentgenol. 2008;190(5):W290–3.PubMedCrossRef Giovanoli O, Heim M, Terracciano L, Bongartz G, Ledermann HP. MRI of hepatic adenomatosis: initial observations with gadoxetic acid contrast agent in three patients. AJR Am J Roentgenol. 2008;190(5):W290–3.PubMedCrossRef
25.
go back to reference Kitao A, Zen Y, Matsui O, Gabata T, Kobayashi S, Koda W, et al. Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR imaging—correlation with molecular transporters and histopathologic features. Radiology. 2010;256(3):817–26.PubMedCrossRef Kitao A, Zen Y, Matsui O, Gabata T, Kobayashi S, Koda W, et al. Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR imaging—correlation with molecular transporters and histopathologic features. Radiology. 2010;256(3):817–26.PubMedCrossRef
26.
go back to reference Leonhardt M, Keiser M, Oswald S, Kühn J, Jia J, Grube M, et al. Hepatic uptake of the magnetic resonance imaging contrast agent Gd-EOB-DTPA: role of human organic anion transporters. Drug Metab Dispos. 2010;38(7):1024–8.PubMedCrossRef Leonhardt M, Keiser M, Oswald S, Kühn J, Jia J, Grube M, et al. Hepatic uptake of the magnetic resonance imaging contrast agent Gd-EOB-DTPA: role of human organic anion transporters. Drug Metab Dispos. 2010;38(7):1024–8.PubMedCrossRef
27.
go back to reference Narita M, Hatano E, Arizono S, Miyagawa-Hayashino A, Isoda H, Kitamura K, et al. Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol. 2009;44(7):793–8.PubMedCrossRef Narita M, Hatano E, Arizono S, Miyagawa-Hayashino A, Isoda H, Kitamura K, et al. Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol. 2009;44(7):793–8.PubMedCrossRef
28.
go back to reference Saito K, Kotake F, Ito N, Ozuki T, Mikami R, Abe K, et al. Gd-EOB-DTPA enhanced MRI for hepatocellular carcinoma: quantitative evaluation of tumor enhancement in hepatobiliary phase. Magn Reson Med Sci. 2005;4(1):1–9.PubMedCrossRef Saito K, Kotake F, Ito N, Ozuki T, Mikami R, Abe K, et al. Gd-EOB-DTPA enhanced MRI for hepatocellular carcinoma: quantitative evaluation of tumor enhancement in hepatobiliary phase. Magn Reson Med Sci. 2005;4(1):1–9.PubMedCrossRef
Metadata
Title
Hepatocyte transporter expression in FNH and FNH-like nodule: correlation with signal intensity on gadoxetic acid enhanced magnetic resonance images
Authors
Norihide Yoneda
Osamu Matsui
Azusa Kitao
Ryuuichi Kita
Kazuto Kozaka
Wataru Koda
Satoshi Kobayashi
Toshifumi Gabata
Hiroko Ikeda
Yasunori Sato
Yasuni Nakanuma
Publication date
01-07-2012
Publisher
Springer Japan
Published in
Japanese Journal of Radiology / Issue 6/2012
Print ISSN: 1867-1071
Electronic ISSN: 1867-108X
DOI
https://doi.org/10.1007/s11604-012-0085-4

Other articles of this Issue 6/2012

Japanese Journal of Radiology 6/2012 Go to the issue