Alpha-Fetoprotein Analysis

Human α-fetoprotein (AFP) is a tumor-associated fetal mammalian glycoprotein involved in ontogenic and oncogenic growth. This tumor marker is encoded by the AFP gene on chromosome 4q25. The fetal protein is a 70-kDa single polypeptide chain containing 3% to 5% carbohydrate. This protein exhibits a triplicate domain structure configured by intramolecular loops dictated by disulfide bridging. AFP occupies an α-1 anodic position in the electrophoretic profile, running slightly slower compared to albumin. AFP is synthesized in the yolk sac, fetal liver, and gastrointestinal tract during pregnancy but is re-expressed in multiple adult tumors of mixed mesodermal or endodermal origin.

In the clinical laboratory, AFP has been employed both as a post-operational tumor marker and as a gestational age-dependent fetal defect marker, demonstrating utility in screening for neural tube defects and aneuploidies. When a fetus has neural tube defects, maternal serum AFP levels are elevated, whereas chromosomal disorders are associated with lower levels. Yolk sac and liver-derived AFP have different carbohydrate content. The half-life of AFP is 4 to 5 days. Similar to albumin, serum AFP binds and transports many ligands such as bilirubin, fatty acids, retinoids, steroids, heavy metals, dyes, flavonoids, phytoestrogens, dioxin, and various drugs.

AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3, based on the reactivity with the lectin lens culinaris agglutinin. AFP-L3 binds strongly to lens culinaris agglutinin through an additional α-1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine, in contrast to the L1 isoform. The L1 isoform is typically associated with non-hepatocellular carcinoma inflammation of the liver disease. The L3 isoform is specific to malignant tumors, and the detected presence can identify patients who need increased monitoring for the development of hepatocellular carcinoma in high-risk populations such as chronic hepatitis B and C and liver cirrhosis.