II. Indications

  1. Pregnancy screening for congenital defect
    1. See Triple Screen
  2. Tumor Marker
    1. Cirrhosis with liver mass (Hepatocellular Carcinoma)
    2. Nonseminomatous germ cell tumor monitoring
      1. AFP used in combination with bHCG

III. Background

  1. Fetal Glycoprotein with molecular weight of 70,000
  2. Sites of synthesis
    1. Embryonic Yolk Sac
    2. Developing Gastrointestinal Tract
    3. Liver
  3. AFP is major Protein in developing fetus
    1. Decreases to undetectable level after birth

IV. Interpretation

  1. Non-pregnant
    1. Normal AFP <5.4 ng/ml (5.4 ug/L)
    2. AFP >500 ng/ml unlikely to be from benign cause
    3. Nonseminomatous germ cell tumor
      1. Poor prognosis if AFP > 10,000 ng/ml at diagnosis
      2. AFP >10,000 associated with 50% five year survival
  2. Normal pregnancy
    1. See Triple Screen for interpretation
    2. Fetal serum AFP: Peaks at 3 mg/ml at 13 weeks
    3. Amniotic fluid AFP: Peaks at 30 ug/ml at 13 weeks
    4. Maternal Serum AFP: Peaks at 100 ng/ml at 30 weeks

V. Causes: Increased AFP in Non-Pregnant States

  1. Benign causes of increased AFP
    1. Cirrhosis
    2. Acute or chronic active Viral Hepatitis
    3. Pregnancy (see below)
  2. Malignant causes of increased AFP
    1. Hepatocellular Carcinoma (usually AFP >1000 ng/ml)
    2. Testicular Cancer (non-seminomatous germ cell tumor)
    3. Gastric Cancer
    4. Biliary cancer
    5. Pancreatic Cancer

VI. Causes: Abnormal Maternal Serum AFP (MSAFP) in Pregnancy

  1. Accurate Pregnancy Dating is critical
    1. AFP interpreted per Gestational age
    2. Incorrect dates is most common cause for abnormal AFP
    3. AFP increases by Gestational age in normal pregnancy
  2. Increased: Fetal malformation
    1. Neural Tube Defect
      1. Anencephaly
      2. Open Spina bifida
    2. Sacrococcygeal Teratoma
    3. Exomphalos
    4. Gastroschisis
    5. Cystic Hygroma
    6. Placental abnormalities
    7. Renal abnormalities
      1. Polycystic Kidney or absent Kidney
      2. Urinary obstruction
      3. Congenital Nephrosis
    8. Osteogenesis imperfecta
    9. Threatened Abortion or Fetal death in utero
    10. Decreased maternal weight or IUGR
    11. Multiple Pregnancy (Twin Gestation)
  3. Decreased
    1. Incorrect Gestational age (older than calculated)
    2. Trisomy 21 (Down Syndrome)
    3. Trisomy 18 (Edward's Syndrome)
    4. Hydatiform mole
    5. Fetal demise
    6. Increased maternal weight

VII. Efficacy: Congenital defect detection in pregnancies

  1. Multiple of median (MOM) cut-off over 2.0 to 2.5
  2. False Positive Rate in normal pregnancies: 5%
  3. Trisomy 21 sensitivity: 21%
  4. Only marker in Triple Screen for Neural Tube Defect
    1. Anencephaly sensitivity: 90%
    2. Spina bifida sensitivity: 80%

VIII. Efficacy: Hepatocellular Carcinoma

  1. Increased in 80% of Hepatocellular Carcinoma cases
  2. Over 1000 ng/ml in 40% of Hepatocellular Carcinoma

IX. Monitoring: Non-seminomatous germ cell tumor

  1. Initial: AFP with bHCG q1-2 months for 1 year
  2. Later: AFP with bHCG q3 months for 1 year

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Related Studies

Ontology: alpha-Fetoproteins (C0002210)

Definition (MSH) The first alpha-globulins to appear in mammalian sera during FETAL DEVELOPMENT and the dominant serum proteins in early embryonic life.
Definition (NCI) Alpha-fetoprotein is a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatoma or teratoma. However, hereditary persistence of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. (from LocusLink)
Definition (NCI_NCI-GLOSS) A protein normally produced by a fetus. AFP levels are usually undetectable in the blood of healthy adult men or women (who are not pregnant). An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor.
Definition (CSP) class of embryonic serum alpha globulins which appear in early development; in adult serum, the presence of AFP indicates certain pathologic states, especially liver neoplasms.
Concepts Biologically Active Substance (T123) , Amino Acid, Peptide, or Protein (T116)
MSH D000509
SnomedCT 49944008, 59386002
LNC LP14331-0, MTHU027153
English alpha Fetoproteins, alpha-Fetoprotein, alpha-Fetoproteins, Fetuins, alpha fetoprotein, fetuin, alpha Foetoprotein, alpha-Fetoproteins [Chemical/Ingredient], alpha foetoprotein, alpha-fetoprotein (AFP), alpha fetoproteins, Alpha fetoproteins, alpha-fetoprotein, Alpha Fetoproteins, alpha Fetoprotein, Fetuin, AFP - Alpha-fetoprotein, Alpha-fetoprotein, Fetuin (substance), alpha Fetoprotein (substance), AFP, Alpha-1-Fetoprotein, Alpha-Fetoglobulin, Alpha-Fetoprotein
German Alphafetoprotein, Alpha-Fetoprotein, AFP, Alpha-Fetoproteine
Swedish Alfafetoproteiner
Czech AFP, alfa-fetoproteiny
Finnish Alfafetoproteiinit
Japanese アルファフェトプロテイン, フェツイン, α-フェトプロテイン, アルファ胎児蛋白質, α-胎児性蛋白質, α-胎児性蛋白, フェチュイン, アルファ-胎児蛋白, アルファ-フェトプロテイン, フェトプロテイン
Spanish alfa-Fetoproteínas, alfa fetoproteína (sustancia), alfa fetoproteína, fetoproteína alfa (sustancia), fetoproteína alfa, fetuína (sustancia), fetuína
French AFP (alpha-FoetoProtéine), Alphafoetoprotéines, Alphafoetoprotéine, alpha-Foetoprotéines
Polish Alfa-fetoproteina
Italian alfa-Fetoproteine
Portuguese alfa-Fetoproteínas