Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

Abstract

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.

Keywords: Alpha-fetoprotein; Alpha-fetoprotein-L3; Cirrhosis; Hepatocellular carcinoma; Hereditary persistence of alpha-fetoprotein; Tumor markers.

Figure 1

ELISA measures. A: ELISA measures alpha-fetoprotein (AFP) by detecting reactivity with two anti-AFP antibodies; B: Interfering antibodies that bind directly to the capture and detect reagents without the target AFP (no analytes). This binding would emit light and become luminescent causing false positive results and high values; C: Interfering antibodies can inhibit reactivity of the ELISA by binding to the reagents and prevent the detection of AFP by the anti-AFP antibodies; that leads to a false negative result. AFP: Alpha-fetoprotein.