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Published in: Journal of Medical Ultrasonics 2/2018

01-04-2018 | Original Article

Association of des-γ-carboxy prothrombin production and Sonazoid-enhanced ultrasound findings in hepatocellular carcinomas of different histologic grades

Authors: Kazumoto Murata, Akiko Saito, Satoshi Katagiri, Shunichi Ariizumi, Masayuki Nakano, Masakazu Yamamoto

Published in: Journal of Medical Ultrasonics | Issue 2/2018

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Abstract

Purpose

We previously reported that hepatocellular carcinoma (HCC) changes to a phenotype producing des-γ-carboxy prothrombin (DCP) during epithelial mesenchymal transition (EMT) in vitro. To confirm this change in vivo, we evaluated the association between DCP production and HCC hemodynamics in patients undergoing resection as EMT and hemodynamic changes are closely associated with each other.

Methods

We evaluated HCC hemodynamics by employing Sonazoid-enhanced ultrasound (SEUS) before surgical resection, and sought associations with histological grade and immunohistochemical staining of DCP in 19 areas from 11 patients.

Results

In 10 HCC areas showing early washout (3 min ≥) using SEUS, three areas corresponded to poorly differentiated HCC and the remaining seven areas corresponded to moderately differentiated HCC, and positive DCP staining was observed in only two of the seven moderately differentiated HCC areas, whereas no staining was observed in poorly differentiated HCC areas. Six HCC areas showing intermediate washout (3–10 min) using SEUS were moderately differentiated, of which five demonstrated positive DCP staining (83.3%, 5/6). However, all HCC areas without enhancement in the arterial phase were well-differentiated and did not show DCP staining.

Conclusion

Our preliminary findings suggest that HCC hemodynamics evaluated by SEUS are associated with histological grade and/or DCP production.
Literature
1.
go back to reference Murata K, Sakamoto A. Impairment of clathrin-mediated endocytosis via cytoskeletal change by epithelial to fibroblastoid conversion in HepG2 cells: a possible mechanism of des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2008;33:1149–55.PubMed Murata K, Sakamoto A. Impairment of clathrin-mediated endocytosis via cytoskeletal change by epithelial to fibroblastoid conversion in HepG2 cells: a possible mechanism of des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2008;33:1149–55.PubMed
2.
go back to reference Murata K, Suzuki H, Okano H, et al. Cytoskeletal changes during epithelial-to-fibroblastoid conversion as a crucial mechanism of des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2009;35:1005–14.CrossRefPubMed Murata K, Suzuki H, Okano H, et al. Cytoskeletal changes during epithelial-to-fibroblastoid conversion as a crucial mechanism of des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2009;35:1005–14.CrossRefPubMed
3.
go back to reference Murata K, Suzuki H, Okano H, et al. Hypoxia-induced des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2010;36:161–70.PubMed Murata K, Suzuki H, Okano H, et al. Hypoxia-induced des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2010;36:161–70.PubMed
4.
go back to reference Suzuki H, Murata K, Gotoh T, et al. Phenotype-dependent production of des-γ-carboxy prothrombin in hepatocellular carcinoma. J Gastroenterol. 2011;46:1219–29.CrossRefPubMed Suzuki H, Murata K, Gotoh T, et al. Phenotype-dependent production of des-γ-carboxy prothrombin in hepatocellular carcinoma. J Gastroenterol. 2011;46:1219–29.CrossRefPubMed
5.
go back to reference Motohara K, Endo F, Matsuda I. Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborn. Lancet. 1985;2:242–4.CrossRefPubMed Motohara K, Endo F, Matsuda I. Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborn. Lancet. 1985;2:242–4.CrossRefPubMed
6.
go back to reference Liebman H, Furie BC, Tong MJ, et al. Des-γ-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984;310:1427–31.CrossRefPubMed Liebman H, Furie BC, Tong MJ, et al. Des-γ-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984;310:1427–31.CrossRefPubMed
7.
go back to reference Hayashi M, Matsui O, Ueda K, et al. Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium. Am J Roentogenol. 1999;172:969–76.CrossRef Hayashi M, Matsui O, Ueda K, et al. Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium. Am J Roentogenol. 1999;172:969–76.CrossRef
8.
go back to reference Pei XQ, Liu LZ, Liu M, et al. Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading. Br J Radiol. 2012;85:e740–7.CrossRefPubMedPubMedCentral Pei XQ, Liu LZ, Liu M, et al. Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading. Br J Radiol. 2012;85:e740–7.CrossRefPubMedPubMedCentral
9.
go back to reference Yanagisawa K, Moriyasu F, Miyahara T, et al. Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol. 2007;33:318–25.CrossRefPubMed Yanagisawa K, Moriyasu F, Miyahara T, et al. Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol. 2007;33:318–25.CrossRefPubMed
10.
go back to reference Claudon M, Dietrich CF, Choi BI, et al. Guidelines and good clinical practice recommendation for contrast enhanced ultrasound (CEUS) in the liver-update 2012; a WFUMB-EFSUMB, AIUM, ASUM, FLAUS and ISUS. Ultrasound Med Biol. 2013;34:187–210.CrossRef Claudon M, Dietrich CF, Choi BI, et al. Guidelines and good clinical practice recommendation for contrast enhanced ultrasound (CEUS) in the liver-update 2012; a WFUMB-EFSUMB, AIUM, ASUM, FLAUS and ISUS. Ultrasound Med Biol. 2013;34:187–210.CrossRef
11.
go back to reference Kudo M. Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol. 2009;44:112–8.CrossRefPubMed Kudo M. Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol. 2009;44:112–8.CrossRefPubMed
12.
go back to reference Matsui O, Kobayashi S, Sanada J, et al. Hepatocellular nodules in liver cirrhosis: hemodynamic evaluation (angiography-assisted CT) with special reference to multi-step hepatocarcinogenesis. Abdom Imaging. 2011;36:264–72.CrossRefPubMedPubMedCentral Matsui O, Kobayashi S, Sanada J, et al. Hepatocellular nodules in liver cirrhosis: hemodynamic evaluation (angiography-assisted CT) with special reference to multi-step hepatocarcinogenesis. Abdom Imaging. 2011;36:264–72.CrossRefPubMedPubMedCentral
13.
go back to reference Korenaga K, Korenaga M, Furukawa M, et al. Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images. J Gastroenterol. 2009;44:733–41.CrossRefPubMed Korenaga K, Korenaga M, Furukawa M, et al. Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images. J Gastroenterol. 2009;44:733–41.CrossRefPubMed
14.
go back to reference Sugimoto K, Moriyasu F, Saito K, et al. Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading. J Ultrasound Med. 2012;31:529–38.CrossRefPubMed Sugimoto K, Moriyasu F, Saito K, et al. Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading. J Ultrasound Med. 2012;31:529–38.CrossRefPubMed
15.
go back to reference Takahashi M, Maruyama H, Ishibashi H, et al. Contrast-enhanced ultrasound with perflubutane microbubble agent: evaluation of differentiation of hepatocellular carcinoma. Am J Roentgenol. 2011;196:W123–31.CrossRef Takahashi M, Maruyama H, Ishibashi H, et al. Contrast-enhanced ultrasound with perflubutane microbubble agent: evaluation of differentiation of hepatocellular carcinoma. Am J Roentgenol. 2011;196:W123–31.CrossRef
16.
go back to reference Tanaka M, Nakashima O, Wada Y, et al. Pathomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver. Hepatology. 1996;24:807–12.CrossRefPubMed Tanaka M, Nakashima O, Wada Y, et al. Pathomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver. Hepatology. 1996;24:807–12.CrossRefPubMed
17.
go back to reference Imai Y, Murakami T, Yoshida S, et al. Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading. Hepatology. 2000;32:205–12.CrossRefPubMed Imai Y, Murakami T, Yoshida S, et al. Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading. Hepatology. 2000;32:205–12.CrossRefPubMed
18.
go back to reference O’Reilly MS, Holmgren L, Chen C, et al. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med. 1996;2:689–92.CrossRefPubMed O’Reilly MS, Holmgren L, Chen C, et al. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat Med. 1996;2:689–92.CrossRefPubMed
19.
go back to reference Yang MH, Wu MZ, Chiou SH, et al. Direct regulation of TWIST by HIF-1α promotes metastasis. Nat Cell Biol. 2008;10:295–305.CrossRefPubMed Yang MH, Wu MZ, Chiou SH, et al. Direct regulation of TWIST by HIF-1α promotes metastasis. Nat Cell Biol. 2008;10:295–305.CrossRefPubMed
20.
go back to reference Sullivan R, Graham CH. Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev. 2007;26:319–31.CrossRefPubMed Sullivan R, Graham CH. Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev. 2007;26:319–31.CrossRefPubMed
21.
go back to reference Zhong H, De Marzo AM, Laughner E, et al. Over expression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res. 1999;59:5830–5.PubMed Zhong H, De Marzo AM, Laughner E, et al. Over expression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res. 1999;59:5830–5.PubMed
Metadata
Title
Association of des-γ-carboxy prothrombin production and Sonazoid-enhanced ultrasound findings in hepatocellular carcinomas of different histologic grades
Authors
Kazumoto Murata
Akiko Saito
Satoshi Katagiri
Shunichi Ariizumi
Masayuki Nakano
Masakazu Yamamoto
Publication date
01-04-2018
Publisher
Springer Japan
Published in
Journal of Medical Ultrasonics / Issue 2/2018
Print ISSN: 1346-4523
Electronic ISSN: 1613-2254
DOI
https://doi.org/10.1007/s10396-017-0816-3

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