Z Gastroenterol 2012; 50 - P5_04
DOI: 10.1055/s-0031-1295960

Impact of tumor markers in diagnosis of patients with hepatocellular carcinoma (HCC) and their clinicopathologic correlation: an interim analysis

D Bettinger 1, M Schultheiß 1, J Bürk 2, E Panther 1, E Knüppel 1, R Küper 3, R Thimme 1, HE Blum 1, HC Spangenberg 1
  • 1Abteilung für Innere Medizin II, Universitätsklinikum Freiburg, Freiburg
  • 2Abteilung für Diagnostische Radiologie und Medizinische Physik, Universitätsklinikum Freiburg, Freiburg
  • 3Wako Chemicals GmbH, Neuss

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and its incidence is rising. Diagnosis is mainly based on ultrasound performance whereas AFP measurement is not recommended according the current AASLD guidelines. The aim of this study is to determine the usefulness of α –fetoprotein (AFP), AFP-L3% and des-γ-carboxyprothrombin (DCP) in diagnosis of HCC and their correlation to clinicopathologic parameters. Methods: Both serum samples of 75 patients with confirmed HCC according the AASLD guidelines receiving transarterial chemoembolisation and of 175 patients with liver cirrhosis without evidence of HCC were prospectively collected. AFP, AFP–L3% and DCP were measured using a micro–total analysis system. Diagnostic accuracy was determined by ROC analysis reporting sensitivity, specificity and the area under the curve (AUC) with 95% confidence interval. Differences in marker values were calculated using non –parametric tests.Results: Optimal cut-off values for AFP, AFP – L3% and DCP were 10 ng/ml, 10% and 2.87 ng/ml with an AUC of 0.745, 0.784 and 0.777 respectively. Combination of all markers showed superior diagnostic accuracy with an AUC of 0.912 and yielded sensitivity and specificity of 93% (87% –99%) and 70% (63%–77%). Regarding patients with AFP < 20 ng/ml AFP-L3% showed sensitivity and specificity of 68% (54%–83%) and 89% (84%–94%) using 10% as the cut-off value. AFP, AFP – L3% and DCP were significantly higher in patients with multilocular HCC (p=0.008, p=0.004 and p=0.011 respectively). Moreover larger tumors and higher BCLC stage were associated with higher DCP values (p=0.042 and p=0.003). Conclusions: Combination of all markers showed a better diagnostic accuracy than using them alone. In patients with AFP < 20ng/ml AFP-L3% can be helpful in diagnosing HCC. DCP yielded a better association with clinicopathologic parameters than AFP and AFP-L3% and may provide further information concerning disease state.

Literatur: 1. Bruix J.Sherman M. (2011), Management of hepatocellular carcinoma: an update. Hepatology, 53: p. 1020-2. 2. Daniele B.,Bencivenga A.,Megna A.S.Tinessa V. (2004), Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology, 127: p. S108-12. 3. Gomaa A.I.,Khan S.A.,Leen E.L.,Waked I.Taylor-Robinson S.D. (2009), Diagnosis of hepatocellular carcinoma. World J Gastroenterol, 15: p. 1301-14. 4. Lee H.S.,Chung Y.H.Kim C.Y. (1991), Specificities of serum alpha-fetoprotein in HBsAg+ and HBsAg- patients in the diagnosis of hepatocellular carcinoma. Hepatology, 14: p. 68-72. 5. Namieno T.,Kawata A.,Sato N.,Kondo Y.Uchino J. (1995), Age-related, different clinicopathologic features of hepatocellular carcinoma patients. Ann Surg, 221: p. 308-14. 6. Tangkijvanich P.,Anukulkarnkusol N.,Suwangool P.,Lertmaharit S.,Hanvivatvong O.,KullavanijayaP.Poovorawan Y. (2000), Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol, 31: p. 302-8. 7. 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: p. 802-7. 8. Yamashita K.,Taketa K.,Nishi S.,Fukushima K.Ohkura T. (1993), Sugar chains of human cord serumalpha-fetoprotein: characteristics of N-linked sugar chains of glycoproteins produced in human liver and hepatocellular carcinomas. Cancer Res, 53: p. 2970-5. 9. Yoshima H.,Mizuochi T.,Ishii M.Kobata A. (1980), Structure of the asparagine-linked sugar chains of alpha-fetoprotein purified from human ascites fluid. Cancer Res, 40: p. 4276-81. 10. Khien V.V.,Mao H.V.,Chinh T.T.,Ha P.T.,Bang M.H.,Lac B.V.,Hop T.V.,Tuan N.A.,Don L.V.,Taketa K.Satomura S. (2001), Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology- proven hepatocellular carcinoma. Int J Biol Markers, 16: p. 105-11. 11. Oda K.,Ido A.,Tamai T.,Matsushita M.,Kumagai K.,Mawatari S.I.,Saishoji A.,Kure T.,Ohno K.,Toyokura E.,Imanaka D.,Moriuchi A.,Uto H.,Oketani M.,Hashiguchi T.Tsubouchi H. (2011), Highly sensitive lens culinaris agglutinin-reactive alpha-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease. Oncol Rep. 12. Carr B.I.,Kanke F.,Wise M.Satomura S. (2007), Clinical evaluation of lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci, 52: p. 776-82. 13. Nouso K.,Kobayashi Y.,Nakamura S.,Kobayashi S.,Takayama H.,Toshimori J.,Kuwaki K.,Hagihara H.,Onishi H.,Miyake Y.,Ikeda F.,Shiraha H.,Takaki A.,Iwasaki Y.,Kobashi H.Yamamoto K. (2011), Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein. J Gastroenterol Hepatol, 26: p. 1195-200. 14. Liebman H.A.,Furie B.C.,Tong M.J.,Blanchard R.A.,Lo K.J.,Lee S.D.,Coleman M.S.Furie B. (1984), Des- gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med, 310: p. 1427-31. 15. Shah D.V.,Engelke J.A.Suttie J.W. (1987), Abnormal prothrombin in the plasma of rats carrying hepatic tumors. Blood, 69: p. 850-4. 16. Shah D.V.,Zhang P.,Engelke J.A.,Bach A.U.Suttie J.W. (1993), Vitamin K-dependent carboxylase activity, prothrombin mRNA, and prothrombin production in two cultured rat hepatoma cell lines. Thromb Res, 70: p. 365-73. 17. Weitz I.C.Liebman H.A. (1993), Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma: a critical review. Hepatology, 18: p. 990-7. 18. Yamaguchi I.,Nakamura K.,Kitano H.,Masuda Y.,Kanke F.,Kobatake S.Satomura S. (2008), Development of des-gamma-carboxy prothrombin (DCP) measuring reagent using the LiBASys clinical analyzer. Clin Chem Lab Med, 46: p. 411-6. 19. Ohhira M.,Saito H.,Suzuki Y.,Naraki T.,Sakurai S.,Ohtake T.,Suzuki M.,FujimotoKohgo Y. (2001), A variant of des-gamma-carboxy prothrombin was increased in alcoholic liver disease without hepatocellular carcinoma. Alcohol Clin Exp Res, 25: p. 46S-50S.