AFP-L3: a new generation of tumor marker for hepatocellular carcinoma

Alpha-fetoprotein (AFP) from hepatocellular carcinoma (HCC) displays differential affinity to lectin Lens culinaris agglutinin (LCA) compared to that from chronic hepatitis/liver cirrhosis. According to their binding capability to LCA, total AFP can be separated into three different glycoforms, AFP-L1, AFP-L2, and AFP-L3. AFP-L1 is the non-LCA-bound fraction, which constitutes the major glycoform of AFP in serum of chronic hepatitis and liver cirrhosis. AFP-L3 is the LCA-bound fraction of AFP. It has been reported that malignant liver cells produce AFP-L3, even when HCC is at its early stages, and especially when the tumor mass is supplied by the hepatic artery. Clinical research has determined that AFP-L3 is a highly specific marker for HCC. The AFP-L3 can be detected in the serum of approximately 35% of the patients with small HCC (<2 cm). The AFP-L3-positive HCC has potential for rapid growth and early metastasis. Compared to imaging techniques, it has been shown to have 9-12 months of lead-time in early HCC recognition. Combined sensitivity of AFP-L3 for HCC is 56%, with a specificity of >95%.Automated assay for measuring AFP-L3 has been developed and introduced in clinical use. The new automated method for measurement of ALP-L3 is based on liquid phase binding of the AFP-L3 glycoform with LCA and two specific monoclonal antibodies labeled with peroxidase and polysulfated tyrosine peptide, respectively.AFP-L3 is a new generation of tumor marker for HCC and yields useful information on HCC for clinical decision making.