Alpha-fetoprotein

Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein or alpha-fetoglobulin) is a protein^[1][2] that in humans is encoded by the AFP gene.^[3][4]

AFP is a major plasma protein produced by the yolk sac and the liver during fetal development that is thought to be the fetal form of serum albumin. The AFP gene is located on the q arm of chromosome 4 (4q25). AFP binds to copper, nickel, fatty acids and bilirubin^[4] and is found in monomeric, dimeric and trimeric forms.

The human fetus has the highest amount of AFP levels found in humans. At the end of the first trimester, fetal AFP levels decrease. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adults is unknown; however, in fetuses it binds estradiol to prevent the transport of this hormone across the placenta. AFP is measured in pregnant women through the analysis of maternal blood or amniotic fluid, as a screening test for a subset of developmental abnormalities: it is principally increased in open neural tube defects and omphalocele & decreased in Down syndrome. It can also be used as a biomarker to detect a subset of tumors in non-pregnant women, men, and children. A level above 500 nanograms/milliliter of AFP in adults can be indicative of hepatocellular carcinoma, germ cell tumors, and metastatic cancers of the liver.

In rats, AFP binds maternal estrogen, preventing its passage through the placenta. The main function of this is to prevent the masculinization of female fetuses. The system can be overridden with massive injections of estrogen, which swamp the AFP system and masculinize female fetuses.

Structure and levels

AFP is a glycoprotein of 591 amino acids and a carbohydrate moiety. Many functions have been proposed for AFP such as an anti-cancer active site peptide has been identified and is referred to as AFPep. In pregnant women, fetal AFP levels can be monitored in urine. AFP is cleared strongly from the kidneys allowing AFP to tend to mirror fetal serum levels. In contrast, maternal serum AFP levels are much lower but continue to rise until about week 32. This is thought to be because the mother is not utilising the AFP, and therefore clears it from her system without issue.

History

LabCorp, a large US clinical laboratory testing company, began offering AFP screening tests in the early 1980s.^[5]

AFP in normal infants

The normal range of AFP for adults and children is variously reported as under 50, under 10, and under 5 ng/mL.^[6][7] At birth, normal infants have AFP levels 4 or more orders of magnitude above this normal range, that decreases to a normal range over the first year of life.^{[8][9][10][11][12][13]} During this time, the normal range of AFP levels spans approximately 2 orders of magnitude.^[10] Correct evaluation of abnormal AFP levels in infants must take into account these normal patterns.^[14]

Very high AFP levels may be subject to hooking (see Tumor marker), resulting in a reported high level that is nonetheless significantly lower than the actual level.^[15] This is important for analysis of a series of AFP tumor marker tests, e.g. in the context of post-treatment early surveillance of cancer survivors, where the rate of decrease of AFP has diagnostic value.

See also

• Tumor marker
• AFP-L3

References

Further reading

External links

• MeSH alpha-Fetoproteins

This article incorporates text from the United States National Library of Medicine, which is in the public domain.