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Value of Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein for Prediction of Hepatocellular Carcinoma Recurrence After Curative Treatment

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Abstract

Background

The fucosylated fraction of alpha-fetoprotein (AFP-L3) has been used as a diagnostic marker for hepatocellular carcinoma (HCC). Recently, a highly sensitive immunoassay using an on-chip electrokinetic reaction and separation by affinity electrophoresis (micro-total analysis system; μTAS) has been developed.

Aim

The aim of this study was to investigate the relationship between changes in the serum AFP-L3 level measured by μTAS assay and recurrence of HCC after curative treatment.

Methods

A total of 414 HCC patients who met the Milan criteria and underwent hepatectomy or radiofrequency ablation were investigated prospectively for the relationship between HCC recurrence and values of tumor markers.

Results

There were significant differences in recurrence-free survival between groups with and without AFP-L3 elevation measured before and after treatment (p = 0.024 and p = 0.001 for before and after treatment, respectively). Multivariate analysis revealed that AFP-L3 status (p = 0.002) measured 1 month after treatment was a significant independent predictor of HCC recurrence after curative treatment.

Conclusions

Elevation of the serum AFP-L3 level before treatment is a predictor of HCC recurrence, and sustained elevation of the AFP-L3 level after treatment is an indicator of HCC recurrence. Repeated measurement of μTAS AFP-L3 should be performed for surveillance of HCC recurrence after curative treatment.

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References

  1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557–2576.

    Article  PubMed  CAS  Google Scholar 

  2. Abelev GI. Production of embryonal serum alpha-globulin by hepatoma: review of experimental and clinical data. Cancer Res. 1968;28:1344–1350.

    PubMed  CAS  Google Scholar 

  3. Conor GI, Tatarinov YS, Abelev GI, Uriel J. A collaborative study for the evaluation of a serologic test for primary liver cancer. Cancer. 1970;25:1091–1098.

    Article  Google Scholar 

  4. Bayati N, Silverman AL, Gordon SC. Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C. Am J Gastroenterol. 1998;93:2452–2456.

    Article  PubMed  CAS  Google Scholar 

  5. Goldstein NS, Blue DE, Hankin R, et al. Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores. Am J Clin Pathol. 1999;111:811–816.

    PubMed  CAS  Google Scholar 

  6. Chu CW, Hwang SJ, Luo JC, et al. Clinical, virologic, and pathologic significance of elevated serum alpha-fetoprotein levels in patients with chronic hepatitis C. J Clin Gastroenterol. 2001;32:240–244.

    Article  PubMed  CAS  Google Scholar 

  7. Aoyagi Y, Suzuki Y, Isemura M, et al. The fucosylation index of alpha-fetoprotein and its usefulness in the early diagnosis of hepatocellular carcinoma. Cancer. 1988;61:769–774.

    Article  PubMed  CAS  Google Scholar 

  8. Aoyagi Y, Saitoh A, Suzuki Y, et al. Fucosylation index of alpha-fetoprotein, a possible aid in the early recognition of hepatocellular carcinoma in patients with cirrhosis. Hepatology. 1993;17:50–52.

    Article  PubMed  CAS  Google Scholar 

  9. Taketa K, Endo Y, Sekiya C, et al. A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res. 1993;53:5419–5423.

    PubMed  CAS  Google Scholar 

  10. Aoyagi Y, Isokawa O, Suda T, et al. The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma. Cancer. 1998;83:2076–2082.

    Article  PubMed  CAS  Google Scholar 

  11. Hayashi K, Kumada T, Nakano S, et al. Usefulness of measurement of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma. Am J Gastroenterol. 1999;94:3028–3033.

    PubMed  CAS  Google Scholar 

  12. Oka H, Saito A, Ito K, et al. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein. J Gastroenterol Hepatol. 2001;16:1378–1383.

    Article  PubMed  CAS  Google Scholar 

  13. Tateishi R, Shiina S, Yoshida H, et al. Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology. 2006;44:1518–1527.

    Article  PubMed  CAS  Google Scholar 

  14. Miyaaki H, Nakashima O, Kurogi M, Eguchi K, Kojiro M. Lens culinaris agglutinin-reactive alpha-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma. J Gastroenterol. 2007;42:962–968.

    Article  PubMed  CAS  Google Scholar 

  15. Tamura Y, Igarashi M, Suda T, et al. Fucosylated fraction of alpha-fetoprotein as a predictor of prognosis in patients with hepatocellular carcinoma after curative treatment. Dig Dis Sci. 2010;55:2095–2101.

    Article  PubMed  CAS  Google Scholar 

  16. Nakamura K, Imajo N, Yamagata Y, et al. Liquid-phase binding assay of alpha-fetoprotein using a sulfated antibody for bound/free separation. Anal Chem. 1998;70:954–957.

    Article  PubMed  CAS  Google Scholar 

  17. Kawabata T, Wada HG, Watanabe M, Satomura S. Electrokinetic analyte transport assay for alpha-fetoprotein immunoassay integrates mixing, reaction and separation on-chip. Electrophoresis. 2008;29:1399–1406.

    Article  PubMed  CAS  Google Scholar 

  18. Kagebayashi C, Yamaguchi I, Akinaga A, et al. Automated immunoassay system for AFP-L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis. Anal Biochem. 2009;388:306–311.

    Article  PubMed  CAS  Google Scholar 

  19. Tamura Y, Igarashi M, Kawai H, Suda T, Satomura S, Aoyagi Y. Clinical advantage of highly sensitive on-chip immunoassay for fucosylated fraction of alpha-fetoprotein in patients with hepatocellular carcinoma. Dig Dis Sci. 2010;55:3576–3583.

    Article  PubMed  CAS  Google Scholar 

  20. Toyoda H, Kumada T, Tada T, et al. Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein <20 ng/ml. Cancer Sci. 2011;102:1025–1031.

    Article  PubMed  CAS  Google Scholar 

  21. Morimoto M, Numata K, Nozaki A, et al. Novel Lens culinaris agglutinin-reactive fraction of α-fetoprotein: a biomarker of hepatocellular carcinoma recurrence in patients with low α-fetoprotein concentrations. Int J Clin Oncol. 2012;17:373–379.

    Article  PubMed  CAS  Google Scholar 

  22. Han SJ, Yoo S, Choi SH, Hwang EH. Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors. Pediatr Surg Int. 1997;12:599–602.

    Article  PubMed  CAS  Google Scholar 

  23. Murray MJ, Nicholson JC. α-fetoprotein. Arch Dis Child Educ Pract Ed. 2011;96:141–147.

    Article  PubMed  CAS  Google Scholar 

  24. Yamamoto K, Imamura H, Matsuyama Y, et al. AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. J Gastroenterol. 2010;45:1272–1282.

    Article  PubMed  CAS  Google Scholar 

  25. Kobayashi M, Hosaka T, Ikeda K, et al. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre- and postoperatively. Hepatol Res. 2011;41:1036–1045.

    Article  PubMed  CAS  Google Scholar 

  26. Toyoda H, Kumada T, Tada T, et al. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy. J Hepatol. 2012;57:1251–1257.

    Article  PubMed  CAS  Google Scholar 

  27. Kanke F, Kumada T, Toyoda H, Satomura S. Reference change values for Lens culinaris agglutinin-reactive α-fetoprotein and des-γ-carboxy prothrombin in patients with chronic hepatitis C. Clin Chem Lab Med. 2012;50:957–960.

    Article  PubMed  CAS  Google Scholar 

  28. Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–121.

    Article  PubMed  CAS  Google Scholar 

  29. Hassan MM, Hwang LY, Hatten CJ, et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002;36:1206–1213.

    Article  PubMed  CAS  Google Scholar 

  30. Yuan JM, Govindarajan S, Arakawa K, Yu MC. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer. 2004;101:1009–1017.

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported in part by a Grant-in-Aid (20390205), Japan Society for the Promotion Science and a Grant-in-Aid from Health, Labor and Welfare, Japan.

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Correspondence to Yasushi Tamura.

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Tamura, Y., Suda, T., Arii, S. et al. Value of Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein for Prediction of Hepatocellular Carcinoma Recurrence After Curative Treatment. Dig Dis Sci 58, 2406–2412 (2013). https://doi.org/10.1007/s10620-013-2661-6

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  • DOI: https://doi.org/10.1007/s10620-013-2661-6

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