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

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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.

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References

  1. 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.

    CAS  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. Motohara K, Endo F, Matsuda I. Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborn. Lancet. 1985;2:242–4.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yanagisawa K, Moriyasu F, Miyahara T, et al. Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol. 2007;33:318–25.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. Kudo M. Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol. 2009;44:112–8.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. Yang MH, Wu MZ, Chiou SH, et al. Direct regulation of TWIST by HIF-1α promotes metastasis. Nat Cell Biol. 2008;10:295–305.

    Article  CAS  PubMed  Google Scholar 

  20. Sullivan R, Graham CH. Hypoxia-driven selection of the metastatic phenotype. Cancer Metastasis Rev. 2007;26:319–31.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan

    Kazumoto Murata

  2. Gastroenterology and Hepatology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo, 150-8935, Japan

    Akiko Saito

  3. Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan

    Satoshi Katagiri, Shunichi Ariizumi, Masayuki Nakano & Masakazu Yamamoto

  4. Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Nasushiobara, Japan

    Kazumoto Murata

Authors
  1. Kazumoto Murata
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  2. Akiko Saito
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  3. Satoshi Katagiri
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  4. Shunichi Ariizumi
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  5. Masayuki Nakano
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  6. Masakazu Yamamoto
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Corresponding author

Correspondence to Akiko Saito.

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Ethics statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for inclusion in this study.

Conflict of interest

The authors have no conflicts of interest to declare.

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Murata, K., Saito, A., Katagiri, S. et al. Association of des-γ-carboxy prothrombin production and Sonazoid-enhanced ultrasound findings in hepatocellular carcinomas of different histologic grades. J Med Ultrasonics 45, 223–229 (2018). https://doi.org/10.1007/s10396-017-0816-3

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  • DOI: https://doi.org/10.1007/s10396-017-0816-3

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