Abstract
Background
We histopathologically examined Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) and protein induced by vitamin K absence (PIVKA) II-positive HCC to clarify the efficacy of these markers for predicting a poor prognosis.
Methods
Serum AFP-L3 and PIVKA II was measured in 110 HCC patients. AFP-L3 was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and PIVKA II by using a high-sensitivity kit. The growth type, capsule formation, capsule infiltration, portal vein invasion, intrahepatic metastasis and histological tumor grade were evaluated pathologically.
Results
Thirty-eight (35%) HCC patients were AFP-L3-positive, and 63 (57%) were PIVKA II-positive. In AFP-L3-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 66% : 42%, P = 0.027) and a poorly differentiated type (positive : negative = 32% : 6%, P < 0.001) were significantly higher than in AFP-L3-negative HCC. In PIVKA II-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 62% : 28%, P < 0.001), vascular invasion (positive : negative = 63% : 26%, P < 0.001), and intrahepatic metastasis (positive : negative = 38% : 4%, P < 0.001) were significantly higher than in PIVKA II-negative HCC. In both AFP-L3- and PIVKA II-positive HCC, the frequency of a poorly differentiated growth type was significantly higher than in HCC positive for either AFP-L3 or PIVKA II or HCC negative for both AFP-L3 and PIVKA II (both positive : either positive : both negative = 37% : 12% : 0%; P = 0.014, P < 0.001, respectively).
Conclusions
AFP-L3 was related to progression from moderately differentiated to poorly differentiated HCC, whereas PIVKA II was more specific to vascular invasion. PIVKA II is therefore likely to be a useful indicator of vascular invasion.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
AM Di Bisceglie JH Hoofnagle (1989) ArticleTitleElevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B Cancer 64 2117–20 Occurrence Handle2478280 Occurrence Handle10.1002/1097-0142(19891115)64:10<2117::AID-CNCR2820641024>3.0.CO;2-7 Occurrence Handle1:STN:280:DyaK3c%2FjtVWjtg%3D%3D
H Oka A Tamori T Kuroki K Kobayashi S Yamamoto (1994) ArticleTitleProspective study of alpha-fetoprotein in cirrhotic patients monitored for development of hepatocellular carcinoma Hepatology 19 61–6 Occurrence Handle7506227 Occurrence Handle1:STN:280:DyaK2c7gt1Ojuw%3D%3D
K Taketa (1990) ArticleTitleAlpha-fetoprotein: reevaluation in hepatology Hepatology 12 1420–32 Occurrence Handle1701754 Occurrence Handle10.1002/hep.1840120625 Occurrence Handle1:CAS:528:DyaK3MXkvV2qtbY%3D
Y Aoyagi M Isemura Y Suzuki C Sekine K Soga T Ozaki et al. (1985) ArticleTitleFucosylated alpha-fetoprotein as marker of early hepatocellular carcinoma Lancet 2 1353–4 Occurrence Handle2415789 Occurrence Handle10.1016/S0140-6736(85)92643-1 Occurrence Handle1:STN:280:DyaL28%2FmsVGlsg%3D%3D
Y Sato K Nakata Y Kato M Shima N Ishii T Koji et al. (1993) ArticleTitleEarly recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein N Engl J Med 328 1802–6 Occurrence Handle7684823 Occurrence Handle10.1056/NEJM199306243282502 Occurrence Handle1:STN:280:DyaK3s3nsFektw%3D%3D
F Yamashita M Tanaka S Satomura K Tanikawa (1996) ArticleTitlePrognostic significance of Lens culinaris agglutinin A-reactive alpha-fetoprotein in small hepatocellular carcinomas Gastroenterology 111 996–1001 Occurrence Handle8831594 Occurrence Handle10.1016/S0016-5085(96)70067-7 Occurrence Handle1:STN:280:DyaK28vivVCqsw%3D%3D
K Hayashi T Kumada S Nakano I Takeda K Sugiyama S Kiriyama et al. (1999) ArticleTitleUsefulness 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 94 3028–33 Occurrence Handle10520864 Occurrence Handle1:STN:280:DyaK1MvkvFWktg%3D%3D
N Yamashiki T Seki M Wakabayashi T Nakagawa M Imamura T Tamai et al. (1999) ArticleTitleUsefulness of Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) as a marker of distant metastasis from hepatocellular carcinoma Oncol Rep 6 1229–32 Occurrence Handle10523686 Occurrence Handle1:STN:280:DyaK1MvlsFWgsA%3D%3D
K Okuda M Tanaka N Kanazawa J Nagashima S Satomura H Kinoshita et al. (1999) ArticleTitleEvaluation of curability and prediction of prognosis after surgical treatment for hepatocellular carcinoma by Lens culinaris agglutinin-reactive alpha-fetoprotein Int J Oncol 14 265–71 Occurrence Handle9917501 Occurrence Handle1:STN:280:DyaK1M7hslGhug%3D%3D
BC Song DJ Suh SH Yang HC Lee YH Chung KB Sung et al. (2002) ArticleTitle Lens culinaris agglutinin-reactive alpha-fetoprotein as a prognostic marker in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization J Clin Gastroenterol 35 398–402 Occurrence Handle12394228 Occurrence Handle10.1097/00004836-200211000-00008 Occurrence Handle1:CAS:528:DC%2BD38XotFKku70%3D
H Fukuda (1998) ArticleTitleTumor vascularity and Lens culinaris agglutinin reactive alpha-fetoprotein are predictors of long-term prognosis in patients with hepatocellular carcinoma after percutaneous ethanol injection therapy Kurume Med J 45 187–93 Occurrence Handle9715046 Occurrence Handle1:CAS:528:DyaK1cXlslGqu7w%3D
R Kuromatsu M Tanaka K Tanikawa (1993) ArticleTitleSerum alpha-fetoprotein and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein in patients with hepatocellular carcinoma Liver 13 177–82 Occurrence Handle7690873 Occurrence Handle1:STN:280:DyaK3szptVantw%3D%3D
T Takayama M Makuuchi S Hirohashi M Sakamoto J Yamamoto K Shimada et al. (1998) ArticleTitleEarly hepatocellular carcinoma as an entity with a high rate of surgical cure Hepatology 28 1241–6 Occurrence Handle9794907 Occurrence Handle10.1002/hep.510280511 Occurrence Handle1:STN:280:DyaK1M%2FhtlyqsQ%3D%3D
K Motohara Y Kuroki H Kan F Endo I Matsuda (1985) ArticleTitleDetection of vitamin K deficiency by use of an enzyme-linked immunosorbent assay for circulating abnormal prothrombin Pediatr Res 19 354–7 Occurrence Handle4000762 Occurrence Handle1:CAS:528:DyaL2MXhvVCisLw%3D Occurrence Handle10.1203/00006450-198519040-00008
S Nagaoka H Yatsuhashi H Hamada K Yano T Matsumoto M Daikoku et al. (2003) ArticleTitleThe des-gamma-carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma Cancer 98 2671–7 Occurrence Handle14669288 Occurrence Handle10.1002/cncr.11839 Occurrence Handle1:CAS:528:DC%2BD2cXit1ygsg%3D%3D
InstitutionalAuthorNameJapan Liver Cancer Study Group (1997) Classification of primary liver cancer Kanehara Tokyo
T Takayama M Makuuchi S Hirohashi M Sakamoto J Yamamoto K Shimada et al. (1998) ArticleTitleEarly hepatocellular carcinoma as an entity with a high rate of surgical cure Hepatology 28 1241–6 Occurrence Handle9794907 Occurrence Handle10.1002/hep.510280511 Occurrence Handle1:STN:280:DyaK1M%2FhtlyqsQ%3D%3D
T Kanai S Hirohashi MP Upton M Noguchi K Kishi M Makuuchi et al. (1987) ArticleTitlePathology of small hepatocellular carcinoma. A proposal for a new gross classification Cancer 60 810–9 Occurrence Handle2439190 Occurrence Handle10.1002/1097-0142(19870815)60:4<810::AID-CNCR2820600417>3.0.CO;2-1 Occurrence Handle1:STN:280:DyaL2s3ktl2msw%3D%3D
AM Hui T Takayama K Sano K Kubota M Akahane K Ohtomo et al. (2000) ArticleTitlePredictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy J Hepatol 33 975–9 Occurrence Handle11131461 Occurrence Handle10.1016/S0168-8278(00)80131-2 Occurrence Handle1:STN:280:DC%2BD3M7it1OntQ%3D%3D
R Izumi K Shimizu T Ii M Yagi O Matsui A Nonomura et al. (1994) ArticleTitlePrognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection Gastroenterology 106 720–7 Occurrence Handle8119543 Occurrence Handle1:STN:280:DyaK2c7msVCqsg%3D%3D
InstitutionalAuthorNameLiver Cancer Study Group of Japan (1994) ArticleTitlePredictive factors for long-term prognosis after partial hepatectomy for patients with hepatocellular carcinoma in Japan. The Liver Cancer Study Group of Japan Cancer 74 2772–80 Occurrence Handle10.1002/1097-0142(19941115)74:10<2772::AID-CNCR2820741006>3.0.CO;2-V
RT Poon ST Fan IO Ng CM Lo CL Liu J Wong (2000) ArticleTitleDifferent risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma Cancer 89 500–7 Occurrence Handle10931448 Occurrence Handle10.1002/1097-0142(20000801)89:3<500::AID-CNCR4>3.0.CO;2-O Occurrence Handle1:STN:280:DC%2BD3cvgt1aktg%3D%3D
Y Koike Y Shiratori S Sato S Obi T Teratani M Imamura et al. (2001) ArticleTitleDes-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 91 561–9 Occurrence Handle11169939 Occurrence Handle10.1002/1097-0142(20010201)91:3<561::AID-CNCR1035>3.0.CO;2-N Occurrence Handle1:CAS:528:DC%2BD3MXhtVKjsLk%3D
A Toyosaka E Okamoto M Mitsunobu T Oriyama N Nakao K Miura (1996) ArticleTitleIntrahepatic metastases in hepatocellular carcinoma: evidence for spread via the portal vein as an efferent vessel Am J Gastroenterol 91 1610–5 Occurrence Handle8759671 Occurrence Handle1:STN:280:DyaK28zit1Wrsw%3D%3D
M Mitsunobu A Toyosaka T Oriyama E Okamoto N Nakao (1996) ArticleTitleIntrahepatic metastases in hepatocellular carcinoma: the role of the portal vein as an efferent vessel Clin Exp Metastasis 14 520–9 Occurrence Handle8970582 Occurrence Handle10.1007/BF00115112 Occurrence Handle1:STN:280:DyaK2s7isFGjtw%3D%3D
H Oka A Saito K Ito T Kumada S Satomura H Kasugai et al. (2001) ArticleTitleMulticenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein J Gastroenterol Hepatol 16 1378–83 Occurrence Handle11851836 Occurrence Handle10.1046/j.1440-1746.2001.02643.x Occurrence Handle1:STN:280:DC%2BD387itVGqtw%3D%3D
K Yamashita K Taketa S Nishi K Fukushima T Ohkura (1993) ArticleTitleSugar chains of human cord serum alpha-fetoprotein: characteristics of N-linked sugar chains of glycoproteins produced in human liver and hepatocellular carcinomas Cancer Res 53 2970–5 Occurrence Handle7686446 Occurrence Handle1:CAS:528:DyaK3sXlslynu7c%3D
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miyaaki, H., Nakashima, O., Kurogi, M. et al. Lens culinaris agglutinin-reactive α-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 42, 962–968 (2007). https://doi.org/10.1007/s00535-007-2117-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-007-2117-x