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

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Abstract
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. 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. 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). 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.