Molecular discrimination between alpha-fetoprotein from patients with hepatocellular-carcinoma and nonneoplastic liver-diseases by their carbohydrate structures (review).

Serum alpha-fetoprotein (AFP) is a good marker of HCC. However, this protein also increases moderately in non-neoplastic liver diseases. The serum concentration of AFP in HCC at the time of initial diagnosis has become lower thanks to the advancement of imaging modalities. These clinical circumstances have lead to the need of molecular discrimination of AFP between HCC and benign liver diseases. This has been attained by taking advantage of the reactivity of AFP with various lectins. The relative amount of the Lens culinaris agglutinin (LCA)-reactive species of AFP is significantly greater in HCC than in benign liver diseases. Molecular basis of this variation is the fucosylation of sugar chain at innermost N-acetyl-glucosamine. On the other hand, the concanavalin A (Con A)-nonreactive species of AFP increases in AFP-producing gastrointestinal carcinoma as compared with HCC and benign liver diseases. Molecular basis of Con A-nonreactive variants is the N-acetylglucosaminylation of the mannose residue at the trimannosyl core, although the position to be modified can be different. Therefore, the terms 'fucosylation and glucosaminylation indices' have been introduced to express the percentages of LCA-reactive and Con A-nonreactive species of AFP, respectively. The reactivity of AFP to erythroagglutinating phytohemagglutinin of Phaseolus vulgaris (E-PHA) also provides useful information for discrimination between HCC and benign liver diseases. These indices together with the measurement of E-PHA molecular variants are useful to detect HCC even if the disease is at an early stage. Furthermore, they seem to serve the prediction of HCC in the follow-up course of chronic liver diseases. Thus, not only qualitative but also quantitative measurements of lectin-based molecular variants of AFP provide us valuable information for the differential diagnosis of various liver diseases.