Alpha-fetoprotein (AFP) is elevated in hepatocellular carcinoma and non-seminomatous germ cell tumours. The biochemical basis for AFP re-expression in HCC is:

• A AFP gene amplification by proto-oncogene activation in hepatocytes
• B AFP is a liver-specific enzyme induced by hepatocyte growth factor (HGF)
• C Dedifferentiation of hepatocytes causing reactivation of fetal gene expression programs ✓
• D Tumour necrosis causes release of AFP stored in hepatocyte lysosomes

Explanation

AFP is a fetal serum glycoprotein produced by the yolk sac and fetal liver (analogue of albumin), normally silenced after birth. In HCC, hepatocytes undergo malignant dedifferentiation (reversion to a fetal/oncofetal phenotype) with reactivation of epigenetically silenced genes including AFP. This is driven by alterations in transcription factors (HNF4A, FoxA2) and epigenetic de-repression. AFP >400 ng/mL with appropriate imaging is diagnostic of HCC without biopsy. AFP is also a marker for endodermal sinus (yolk sac) tumours (germ cell tumours), where it is produced by yolk sac elements recapitulating embryonic AFP production.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.