Skip to main content
Log in

Clinical Evaluation of Lens Culinaris Agglutinin-Reactive α-Fetoprotein and Des-γ-Carboxy Prothrombin in Histologically Proven Hepatocellular Carcinoma in the United States

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

There is no established clinical role for the lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) and des-γ-carboxy prothrombin (DCP) in the management of the U.S. hepatocellular carcinoma (HCC) patient population. In order to clarify the clinical usefulness and characteristics of AFP-L3% and DCP, a prospective study was performed on United States patients having histologically proven hepatocellular carcinoma. Ninety-nine histologically proven HCC patients, who were diagnosed with unresectable cancer between July 1999 and March 2001 at the Liver Cancer Center of the University of Pittsburgh Medical Center, were included for analysis. The sensitivity of AFP-L3%, DCP, and AFP was 61.6%, 72.7%, and 67.7%, respectively. The highest sensitivity, 85.9%, was obtained in the combination of three markers. Statistically significant differences were observed for portal vein invasion in AFP-L3% and AFP levels (P=0.0059 and P=0.0360, respectively). DCP was significantly associated with metastasis (P=0.0368). There were significant associations between AFP-L3% and AFP results and patient survival (P=0.0150 and P=0.0020, respectively). AFP-L3%, platelet count,and albumin showed a significant difference with respect to outcomes on Cox’s proportional hazard model (P=0.0059, P=0.0073, and P=0.0265, respectively). The combination of AFP-L3%, DCP, and AFP was determined to be superior for detection of HCC compared with each marker alone or to other combinations. AFP-L3% was significantly related to portal vein invasion and patient outcomes and appears to be a useful prognostic marker for HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden globocan 2000. Int J Cancer 94:153–156

    Article  PubMed  CAS  Google Scholar 

  2. El-Serag HB (2004) Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127:S27–S34

    Article  PubMed  Google Scholar 

  3. Zaman SN, Melia WM, Johnson RD, Portmann BC, Johnson PJ, Williams R (1985) Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients. Lancet 1:1357–1360

    Article  PubMed  CAS  Google Scholar 

  4. Poynard T, Aubert A, Lazizi Y, et al (1991) Independent risk factors for hepatocellular carcinoma in French drinkers. Hepatology 13:896–901

    Article  PubMed  CAS  Google Scholar 

  5. Colombo M, Franchis Rd, Ninno ED, et al. (1991) Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 325:675–680

    Article  PubMed  CAS  Google Scholar 

  6. Tsukuma H, Hiyama T, Tanaka S, et al. (1993) The factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328:1797–1801

    Article  PubMed  CAS  Google Scholar 

  7. Chevret S, Trinchet JC, Mathieu D, Rached AA, Beaugrand M, Chastang C (1999) A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. J Hepatol 31:133–141

    Article  PubMed  CAS  Google Scholar 

  8. Bruix J SMPGC, American Association for the Study of Liver Diseases (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236

    Article  Google Scholar 

  9. Shinagawa T, Ohto M, Kimura K, et al. (1984) Diagnosis and clinical features of small hepatocellular carcinoma eith emphasis on the utility of real-time ultrasonography. Gastroenterology 86:495–502

    PubMed  CAS  Google Scholar 

  10. Ikeda K, Saitoh S, Koida I, et al. (1993) Diagnosis and follow-up of small hepatocellular carcinoma with selective intraarterial digital subtraction angiography. Hepatology 17:1003–1007

    Article  PubMed  CAS  Google Scholar 

  11. Oka H, Tamori A, Kuroki T, Kobayashi K, Yamamoto S (1994) Prospective study of α-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma. Hepatology 19:61–66

    Article  PubMed  CAS  Google Scholar 

  12. Takayasu K, Moriyama N, Muramatsu Y, et al. (1990) The diagnosis of small hepatocellular carcinoma: efficacy of various imaging procedures in 100 patients. AJR 155:49–54

    PubMed  CAS  Google Scholar 

  13. Takayasu K, Furukawa H, Wakao F, et al. (1995) CT diagnosis of early hepatocellular carcinoma: sensitivity, findings, and CT-pathologic correlation. AJR 164:885–890

    PubMed  CAS  Google Scholar 

  14. Ebara M, Ohto M, Watanabe Y, et al. (1986) Diagnosis of small hepatocellular carcinoma: Correlation of MR imaging and tumor histologic studies. Radiology 159:371–377

    PubMed  CAS  Google Scholar 

  15. Daniele B, Bencivenga A, Megna AS, Tinessa V (2004) α-Fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology 127:S108–S12

    Article  PubMed  Google Scholar 

  16. Bruix J, Sherman M, Llovet JM, et al. (2001) Clinical management of hepatocellular carcinoma. Conclusion of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430

    Article  PubMed  CAS  Google Scholar 

  17. Sheu JC, Sung JL, Chen DS, et al. (1985) Early detection of hepatocellular carcinoma by real-time ultrasonography. A prospective study. Cancer 56:660–666

    Article  PubMed  CAS  Google Scholar 

  18. Taketa K, Sekiya C, Namiki M, et al. (1990) Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology 99:508–518

    PubMed  CAS  Google Scholar 

  19. Taketa K, Endo Y, Sekiya C, et al. (1993) A collaborative study for the evaluation of lectin-reactive a-fetoproteins in early detection of hepatocellular carcinoma. Cancer Res 53:19–23

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Sato Y, Nakata K, Kato Y, et al. (1993) Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med 328:1802–1806

    Article  PubMed  CAS  Google Scholar 

  22. Shiraki K, Takase K, Tameda Y, Hamada M, Kosaka Y, Nakano T (1995) A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Hepatology 22:802–807

    Article  PubMed  CAS  Google Scholar 

  23. Yamashita F, Tanaka M, Satomura S, Tanikawa K (1995) Monitoring of lectin-reactive a-fetoprotein in patients with hepatocellular carcinoma treated using transcatheter arterial embolization. Eur J Gastroenterol Hepatol 7:627–633

    PubMed  CAS  Google Scholar 

  24. Yamashita F, Tanaka M, Satomura S, Tanikawa K (1996) Prognostic significance of lens culinaris agglutinin A-reactive a-fetoprotein in small hepatocellular carcinomas. Gastroenterology 111:996–1001

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Kumada T, Nakano S, Takeda I, et al. (1999) Clinical utility of lens culinaris aggulutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis. J Hepatol 30:125–130

    Article  PubMed  CAS  Google Scholar 

  27. Tanaka M, Saito A, Ito K, et al. (2000) Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is the most significant prognostic factor for hepatocellular carcinoma after therapy. Hepatology 34:233A

    Google Scholar 

  28. Tada T, Kumada T, Toyoda H, et al. (2005) Relationship between lens culinaris agglutinin-reactive α-fetoprotein and pathologic features of hepatocellular carcinoma. Liver Int 25:1–6

    Article  CAS  Google Scholar 

  29. Ono M, Ohta H, Ohhira M, Sekiya C, Namiki M (1990) Measurement of immunoreactive prothrombin precursor and vitamin-K dependent gamma-carboxylation in human hepatocellular carcinoma tissues: decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxyprothrombin synthesis. Tumor Biol 11:319–326

    Article  CAS  Google Scholar 

  30. Liebman HA (1989) Isolation and characterization of a hepatoma-associated abnormal (des-gamma carboxy) prothrombin. Cancer Res 49:6493–6497

    PubMed  CAS  Google Scholar 

  31. Aoyagi Y, Oguro M, Yanagi M, et al. (1996) Clinical significance of simultaneous determination of alpha-fetoprotein and des-gamma carboxyprothrombin in monitoring recurrence in patients with hepatocellular carcinoma. Cancer 77:1781–1786

    Article  PubMed  CAS  Google Scholar 

  32. Mita Y, Aoyagi Y, Yanagi M, Suda T, Suzuki Y, Asakura H (1998) The usefulness of determining des-gamma carboxyprothrombin by sensitive enzyme immunoassay in the early diagnosis of patients with hepatocellular carcinoma. Cancer 82:1643–1648

    Article  PubMed  CAS  Google Scholar 

  33. Nomura F, Ishijima M, Kuwa K, Tanaka N, Nakai T, Ohnishi K (1999) Serum des-gamma carboxyprothrombin levels determined by a new generation of sensitive immunoassay in patients with small-sized hepatocellular carcinoma. Am J Gastroenterol 94:650–654

    Article  PubMed  CAS  Google Scholar 

  34. Izuno K, Fujiyama S, Yamasaki K, Sato M, Sato T (1995) Early detection of hepatocellular carcinoma associated with cirrhosis by combined assay of des-gamma carboxy prothrombin and alpha-fetoprotein: a prospective study. Hepatogastroenterology 42:387–393

    PubMed  CAS  Google Scholar 

  35. Ikoma J, Kaito M, Ishihara T, et al. (2002) Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum des-gamma carboxy prothrombin: a prospective study. Hepatogastroenterology 49:235–238

    PubMed  CAS  Google Scholar 

  36. Shimauchi Y, Tanaka M, Kuromatsu R, et al. (2000) A simultaneous monitoring of lens culinaris aggulutinin A-reactive alpha-fetoprotein and des-gamma carboxyprothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients. Oncol Rep 7:249–256

    PubMed  CAS  Google Scholar 

  37. Ishii M, Gama H, Chida N, et al. (2000) Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. Am J Gastroenterol 95:1036–1040

    PubMed  CAS  Google Scholar 

  38. Fujiyama S, Tanaka M, Maeda S, Ashihara H, Hirata R, Tomita K (2002) Tumor markers in early diagnosis, follow-up and management of patients with hepatocellular carcinoma. Oncology 62:57–63

    Article  PubMed  CAS  Google Scholar 

  39. Okuda H, Nakanishi T, Takatsu K, et al. (2002) Clinicopathologic features of patients with hepatocellular carcinoma seropositive for a-fetoprotein-L3 and seronegative for des-g-carboxy prothrombin in comparison with those seropositive for des-g-carboxy prothrombin alone. J Gastroenterol Hepatol 17:772–778

    Article  PubMed  CAS  Google Scholar 

  40. Okuda H, Saito A, Haruyama K, et al. (2004) Unique clinicaopathological features of patients with primary malignant hepatic tumors who are seropositive for lectin-reactive α-fetoprotein alone: report of five cases. J Gastroenterol Hepatol 19:113–119

    Article  PubMed  Google Scholar 

  41. Okuda H, Saito A, Shiratori K, Yamamoto M, Takasaki K, Nakano M (2005) Clinicopathologic feature of patients with primary malignant hepatic tumors seropositive for a-fetoprotein-L3 alone in comparison with other patients seropositive for a-fetoprotein-L3. J Gastroenterol Hepatol 20:759–764

    Article  PubMed  Google Scholar 

  42. Katoh H, Nakamura K, Tanaka T, Satomura S, Matsuura S (1998) Automatic and simultaneous analysis of Lens culinaris agglutinin-reactive alpha-fetoprotein ratio and total alpha-fetoprotein concentration. Anal Chem 70:2110–2114

    Article  PubMed  CAS  Google Scholar 

  43. Yamagata Y, Katoh H, Nakamura K, Tanaka T, Satomura S, Matsuura S (1998) Determination of alpha-fetoprotein concentration based on liquid-phase binding assay using anion exchange chromatography and sulfated peptide introduced antibody. J Immunol Methods 212:161–168

    Article  PubMed  CAS  Google Scholar 

  44. Yamagata Y, Shimizu K, Nakamura K, et al. (2003) Simultaneous determination of percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein and alpha-fetoprotein concentration using the LiBASys clinical auto-analyzer. Clin Chim Acta 327:59–67

    Article  PubMed  CAS  Google Scholar 

  45. El-Serag HB, Mason AC, Key C (2001) Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 33:62–65

    Article  PubMed  CAS  Google Scholar 

  46. Hamamura K, Shiratori Y, Shiina S, et al. (2000) Unique clinical characteristics of patients with hepatocellular carcinoma who present with plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer 88:1557–1564

    Article  PubMed  CAS  Google Scholar 

  47. Koike Y, Shiratori Y, Sato S, et al. (2001) Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 91:561–569

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported in part by NIH Grant CA 82723 (to B.I.C.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brian I. Carr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carr, B.I., Kanke, F., Wise, M. et al. Clinical Evaluation of Lens Culinaris Agglutinin-Reactive α-Fetoprotein and Des-γ-Carboxy Prothrombin in Histologically Proven Hepatocellular Carcinoma in the United States. Dig Dis Sci 52, 776–782 (2007). https://doi.org/10.1007/s10620-006-9541-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9541-2

Keywords

Navigation