AFP

by Assia Bassarova

Background

Alpha-fetoprotein (AFP) is an oncofetal protein found in high concentrations in fetal and maternal blood and in patients with certain neoplastic and non-neoplastic disorders. AFP is a single-chain sialylated glycoprotein. Synthesis of AFP by the human embryo can be detected as early as 29 days after conception. Initially it is produced by both the yolk sac and liver, but hepatic production increases steadily until, by the end of the first trimester, it is nearly all synthesized there. AFP levels in fetal serum reach a maximum at about 14th week of gestation. The function of AFP is not fully known. The close similarity between albumin and AFP have suggested that AFP could be a precursor to albumin. The close conservation of AFP through phylogeny suggests some function essential to the fetus and not performed by albumin. It has been suggested that AFP plays a role in estrogen binding, immunoregulation or binding of bilirubin, but so far none of those is confirmed.

Staining in normal cells/tissues

fetal liver and the endoderm of the yolk sac. Positivity in non-neoplastic liver diseases (hepatitis, cirrhosis) is reported.

Staining in tumors

  • Present in yolk sac (endodermal sinus) tumors of testis and ovary and in a proportion of other germ cell tumors. However, the staining even in yolk sac tumors may be limited and the sensitivity is low.
  • Embryonal carcinoma (usually focal <20% cases).
  • Hepatocellular carcinoma (>60%) and hepatoblastoma (>80%).
  • Sialoblastoma is reported positive in majority of cases.
  • Alpha-fetoprotein may also be secreted by other types of tumors, including carcinomas especially with hepatoid differentiation of different organs including stomach, colon, pancreas and lung.

Staining pattern

Moderate to strong, cytoplasmic, granular staining often with accentuated cell membranes.

Control tissue

Yolk sac tumor or fetal liver.

Application

  • Identification and differential diagnosis of hepatocellular carcinoma.  AFP has a low sensitivity for this tumor, but high specificity and may be useful in poorly differentiated tumors, which are more often positive for AFP but may lack the characteristic canalicular pattern with p-CEA and CD10. It should be used in panel with other markers (e.g. Hepatocyte Ag, p-CEA, CD10, Cytokeratins 7, 19, 20 or GLP3).
  • Subtyping of testicular and ovarian germ cell tumors. Recommended to use in combination with other markers e.g. low molecular weight cytokeratins, PLAP, CD30, beta-HCG, OCT4 or SALL4.
  • Confirmation of hepatoid differentiation in carcinomas.

Selected references