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Evaluation of seven different staging systems for alpha-fetoprotein expression in hepatocellular carcinoma after hepatectomy

Tumor Biology volume 34, pages 1061–1070 (2013)Cite this article

Abstract

Alpha-fetoprotein (AFP) represents the most important biomarker for hepatocellular carcinoma (HCC). The aim of this study was to identify the optimal staging system to predict the survival of AFP-negative and AFP-positive patients. This study analyzed the data of 431 AFP-negative HCC patients who had previously undergone surgery and 471 AFP-positive HCC candidates. Kaplan–Meier (K-M) survival estimates were plotted, and the P values were assessed using log-rank tests. The Akaike information criterion (AIC) was calculated using the results of a Cox’s regression to compare the overall assessment of the seven different staging systems. The AFP-positive group displayed characteristics of poor tumor biological behavior (tumor multiplicity [P = 0.032], low grade differentiation [P = 0.000] and carcinoma cell embolus [P = 0.031]), poor liver function (Child–Pugh B classification [P = 0.003], abnormal prothrombin time activity [P = 0.037] and moderate/severe cirrhosis [P = 0.000]) and increased operative difficulties (transfusion; P = 0.001). TNM7th staging showed the lowest AIC value (1,279.528) for the AFP-negative group, while the Barcelona Clinic Liver Cancer (BCLC) staging system revealed the lowest AIC value (1,991.233) for the AFP-positive group. In conclusion, among the seven favorable staging systems, BCLC staging was superior for the AFP-positive group, while the TNM7th was a more appropriate staging model for the AFP-negative group.

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References

  1. Hsu CY, Hsia CY, Huang YH, Su CW, Lin HC, Lee PC, et al. Selecting an optimal staging system for hepatocellular carcinoma: comparison of 5 currently used prognostic models. Cancer. 2010;116(12):3006–14.

    PubMed  Article  Google Scholar 

  2. Jiang X, Pan SY, de Groh M, Liu S, Morrison H. Increasing incidence in liver cancer in Canada, 1972–2006: age–period–cohort analysis. J Gastrointest Oncol. 2011;2(4):223–31.

    PubMed  Google Scholar 

  3. Primary Liver Cancer Diagnosis and Treatment Expert Panel of the Chinese Ministry of Health. Guidelines on the diagnosis and treatment of primary liver cancer (2011 edition). Chin Clin Oncol. 2012;1(1):10.

    Google Scholar 

  4. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    PubMed  Article  Google Scholar 

  5. Bergstrand CG, Czar B. Paper electrophoretic study of human fetal serum proteins with demonstration of a new protein fraction. Scand J Clin Lab Invest. 1957;9(3):277–86.

    PubMed  Article  CAS  Google Scholar 

  6. De Minicis S, Marzioni M, Saccomanno S, Rychlicki C, Agostinelli L, Trozzi L, et al. Cellular and molecular mechanisms of hepatic fibrogenesis leading to liver cancer. Transl Gastrointest Cancer. 2012;1(1):88–94.

    Google Scholar 

  7. Gillespie JR, Uversky VN. Structure and function of alpha-fetoprotein: a biophysical overview. Biochim Biophys Acta. 2000;1480(1–2):41–56.

    PubMed  Article  CAS  Google Scholar 

  8. Debruyne EN, Delanghe JR. Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta. 2008;395(1–2):19–26.

    PubMed  Article  CAS  Google Scholar 

  9. Lee KH, Wu CJ, Wang CC, Hung JH. Prevention of chronic HBV infection induced hepatocellular carcinoma development by using antiplatelet drugs. Hepatobiliary Surg Nutr. 2012;1(1):57–8.

    Google Scholar 

  10. Kao WY, Su CW, Chau GY, Lui WY, Wu CW, Wu JC. A comparison of prognosis between patients with hepatitis B and C virus-related hepatocellular carcinoma undergoing resection surgery. World J Surg. 2011;35(4):858–67.

    PubMed  Article  Google Scholar 

  11. Gupta S, Bent S, Kohlwes J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med. 2003;139(1):46–50.

    PubMed  CAS  Google Scholar 

  12. Zhang XF, Qi X, Meng B, Liu C, Yu L, Wang B, et al. Prognosis evaluation in alpha-fetoprotein negative hepatocellular carcinoma after hepatectomy: comparison of five staging systems. Eur J Surg Oncol. 2010;36(8):718–24.

    PubMed  Article  Google Scholar 

  13. Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer. 2004;112(1):44–50.

    PubMed  Article  CAS  Google Scholar 

  14. Changchien CS, Chen CL, Yen YH, Wang JH, Hu TH, Lee CM, et al. Analysis of 6381 hepatocellular carcinoma patients in southern Taiwan: prognostic features, treatment outcome, and survival. J Gastroenterol. 2008;43(2):159–70.

    PubMed  Article  CAS  Google Scholar 

  15. Japan LCSGi. Survey and follow-up study of primary liver cancer in Japan — report 11. Kanzo. 1995;36:208–18.

    Article  Google Scholar 

  16. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28(3):751–5.

  17. Hu KQ, Kyulo NL, Lim N, Elhazin B, Hillebrand DJ, Bock T. Clinical significance of elevated alpha-fetoprotein (AFP) in patients with chronic hepatitis C, but not hepatocellular carcinoma. Am J Gastroenterol. 2004;99(5):860–5.

    PubMed  Article  CAS  Google Scholar 

  18. Yen YH, Changchien CS, Wang JH, Kee KM, Hung CH, Hu TH, et al. A modified TNM-based Japan Integrated Score combined with AFP level may serve as a better staging system for early-stage predominant hepatocellular carcinoma patients. Dig Liver Dis. 2009;41(6):431–41.

    PubMed  Article  Google Scholar 

  19. Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, et al. Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology. 2005;41(4):707–16.

    PubMed  Article  Google Scholar 

  20. Kim BK, Kim SU, Park JY, Kim DY, Ahn SH, Park MS, et al. Applicability of BCLC stage for prognostic stratification in comparison with other staging systems: single centre experience from long-term clinical outcomes of 1717 treatment-naïve patients with hepatocellular carcinoma. Liver Int. 2012. 10.1111/j.1478-3231.2012.02811.x.

  21. Edge SB CM, Carducci MA, Compton CC, et al. AJCC cancer staging manual. 7th ed. Chicago: Springer; 2009. p. 237.

    Google Scholar 

  22. Kudo M, Chung H, Haji S, Osaki Y, Oka H, Seki T, et al. Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score. Hepatology. 2004;40(6):1396–405.

    PubMed  Article  Google Scholar 

  23. Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M. Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg. 2007;245(6):909–22.

    PubMed  Article  Google Scholar 

  24. Collette S, Bonnetain F, Paoletti X, Doffoel M, Bouché O, Raoul JL, et al. Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials. Ann Oncol. 2008;19(6):1117–26.

    PubMed  Article  CAS  Google Scholar 

  25. Llovet JM, Bruix J. Prospective validation of the Cancer of the Liver Italian Program (CLIP) score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology. 2000;32(3):679–80.

    PubMed  Article  CAS  Google Scholar 

  26. Ueno S, Tanabe G, Sako K, Hiwaki T, Hokotate H, Fukukura Y, et al. Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program. Hepatology. 2001;34(3):529–34.

    PubMed  Article  CAS  Google Scholar 

  27. Marrero JA, Kudo M, Bronowicki JP. The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist. 2010;15 Suppl 4:23–33.

    PubMed  Article  CAS  Google Scholar 

  28. Yang T, Zhang J, Lu JH, Yang LQ, Yang GS, Wu MC, et al. A new staging system for resectable hepatocellular carcinoma: comparison with six existing staging systems in a large Chinese cohort. J Cancer Res Clin Oncol. 2011;137(5):739–50.

    PubMed  Article  Google Scholar 

  29. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56(4):918–28.

    PubMed  Article  CAS  Google Scholar 

  30. Chevret S, Trinchet JC, Mathieu D, Rached AA, Beaugrand M, Chastang C. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. J Hepatol. 1999;31(1):133–41.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgment

This work was supported by grants from the State Key Project on Infectious Diseases of China (China National Science and Technology Major Project Grant No. 2008ZX10002-025; 2012ZX10002-016).

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Affiliations

  1. Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China

    Jianguo Zhou, Tao Yan, Xinyu Bi, Hong Zhao, Zhen Huang, Yefan Zhang, Yuan Li, Li Feng, Jing Wang & Jianqiang Cai

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  1. Jianguo Zhou
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  2. Tao Yan
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  4. Hong Zhao
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  7. Yuan Li
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Correspondence to Jing Wang or Jianqiang Cai.

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J. Zhou, T. Yan and X. Bi contributed equally to this study.

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Zhou, J., Yan, T., Bi, X. et al. Evaluation of seven different staging systems for alpha-fetoprotein expression in hepatocellular carcinoma after hepatectomy. Tumor Biol. 34, 1061–1070 (2013). https://doi.org/10.1007/s13277-013-0646-x

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  • DOI: https://doi.org/10.1007/s13277-013-0646-x

Keywords

  • Hepatocellular carcinoma
  • Alpha-fetoprotein
  • Clinical staging system
  • Survival