Stains & CD markers
Alpha fetoprotein (AFP)

Editor-in-Chief: Debra L. Zynger, M.D.
João Lobo, M.D.
Rui Henrique, M.D., Ph.D.

Last author update: 20 April 2020
Last staff update: 18 June 2021

Copyright: 2003-2024,, Inc.

PubMed Search: Alpha fetoprotein[TI] review[PT] pathology

João Lobo, M.D.
Rui Henrique, M.D., Ph.D.
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Cite this page: Lobo J, Henrique R. Alpha fetoprotein (AFP). website. Accessed May 19th, 2024.
Definition / general
  • Alpha fetoprotein is a marker related to embryonic development (yolk sac), mainly used for diagnosing germ cell tumors and liver tumors
  • Overall specific but not sensitive marker
Essential features
  • Positive immunostaining in a subset of hepatocellular carcinomas and hepatoblastomas but also found to be positive in other liver diseases
  • Positive immunostaining can be found in the various patterns of yolk sac tumor but also can be positive in teratoma
  • Positive in various tumors with hepatoid differentiation
Clinical features
  • High serum levels in several conditions:
  • Specific serum isoforms: L1, in nonneoplastic liver disease; L2, in yolk sac tumor; L3, in liver cancer
    • Both L2 and L3 can be elevated in pediatric yolk sac tumor, reflecting both yolk sac and hepatic differentiation (J Pediatr Surg 1989;24:350)
  • Elevations in maternal serum and amniotic fluid may indicate fetal abnormalities, including neural tube defects (Am J Obstet Gynecol 2006;195:1623)
  • Serum levels drop after birth (still elevated until around 6 months of age, needing care in interpretation); small amounts still produced in adults (Annu Rev Med 1977;28:453)
  • Serum AFP increases in 50 - 70% of patients with nonseminoma germ cell tumors; half life is 5 to 7 days; prominent elevations in pure seminomas usually indicate yolk sac differentiation in metastatic locations; patients should be treated as having mixed germ cell tumor (Nat Rev Urol 2020;17:201)
  • Membranous or cytoplasmic staining is expected; granular
Uses by pathologists
  • Supporting the diagnosis of germ cell tumors (testicular, ovarian or extragonadal), especially those with identifiable yolk sac tumor foci (Mod Pathol 2005;18:S61)
  • Supporting the diagnosis of hepatocellular disease (including nonneoplastic diseases such as chronic hepatitis, and neoplastic diseases such as hepatocellular carcinoma and hepatoblastoma) (World J Gastroenterol 2005;11:5015)
  • Confirming suspected hepatoid foci within other neoplasms or confirming that tumor cells produce AFP in case of remarkable elevations of this marker in patient serum (Mod Pathol 1997;10:686)
Prognostic factors
Microscopic (histologic) images

Contributed by João Lobo, M.D., Rui Henrique, M.D., Ph.D.

Prepubertal testicular yolk sac tumor

Prepubertal testicular yolk sac tumor, AFP

Prepubertal testicular yolk sac tumor

Prepubertal testicular yolk sac tumor, AFP

Metastatic yolk sac tumor

Metastatic yolk sac tumor, AFP

Testicular mixed germ cell tumor

Testicular mixed germ cell tumor, AFP

Fetal liver

Fetal liver, AFP


Hepatoblastoma, AFP

Virtual slides

Images hosted on other servers:

Ovarian yolk sac tumor, AFP

Yolk sac tumor in undescended testis, AFP

Positive staining - normal
  • Well fixed and nonautolyzed embryonal liver is a reliable positive control
  • Early gut, yolk sac; nonspecific background reaction frequent in necrotic and cystic areas, since it is a protein secreted in serum (Int J Dev Biol 2012;56:755)
  • Low expression in normal adult liver (EBioMedicine 2018;33:57)
Positive staining - disease
Negative staining
  • Germ cell neoplasia in situ (GCNIS)
  • Seminoma
  • Embryonal carcinoma
  • Choriocarcinoma
  • Gonadoblastoma
  • Spermatocytic tumor
  • Teratoma: can be positive in some epithelial components (20%) (Acta Pathol Microbiol Immunol Scand A 1983;91:165)
  • Hepatoblastoma (15%): not significantly associated with subtype (Eur J Cancer 2012;48:1853)
  • Cholangiocarcinoma
  • Metastatic adenocarcinomas to the liver (5%)
Board review style question #1

Which of the following is true about the immunohistochemical expression of AFP?

  1. It can be positive in other liver diseases besides hepatocellular carcinoma and hepatoblastoma
  2. It is more sensitive than glypican 3 for diagnosing yolk sac tumor
  3. Nuclear staining is expected
  4. Seminomas are typically positive
  5. Teratomas are invariably negative
Board review style answer #1
A. It can be positive in other liver diseases besides hepatocellular carcinoma and hepatoblastoma. It is a specific marker but less sensitive than glypican 3. Seminomas are typically negative. Cytoplasmic or membrane staining is expected. Teratomas may show positivity in certain epithelial elements. Other liver diseases and liver tumors can show positive immunostaining, including metastatic disease to the liver.

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