Alpha-fetoprotein

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Alpha-fetoprotein
RNA expression pattern

Alpha-fetoprotein (AFP, -fetoprotein) is a protein[1][2] that in humans is encoded by the AFP

gene.[3][4]
This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the
liver during fetal life. The protein is thought to be the fetal counterpart of serum albumin, and the
alpha-fetoprotein and albumin genes are present in tandem on chromosome 4. Alpha-fetoprotein
is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty
acids and bilirubin.[4]
The human fetus has the highest amount of AFP levels found in humans. These AFP levels
gradually decrease after birth down to the low, but detectable levels found in adults by the time a
newborn reaches 8 to 12 months. AFP has no known function in healthy adults. In normal
fetuses, AFP binds the hormone estradiol. AFP is measured in pregnant women, using 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 omphalocoele & decreased in Down
syndrome. It is also measured in non-pregnant women, other adults, and children, serving as a
biomarker to detect a subset of tumors. In adults, levels over 500 nanograms/milliliter of AFP are
seen in only three situations: Hepatocellular carcinoma, Germ cell tumors, and metastatic cancer
in the liver originating from other primary tumors elsewhere.
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. AFP is normally produced by the fetal yolk sac, the fetal gastrointestinal tract, and
eventually by the fetal liver. Levels of AFP in fetal serum rise until the end of the first trimester
of gestation and then fall. Because the fetus excretes AFP into its urine, amniotic fluid levels of
AFP tend to mirror fetal serum levels. In contrast, maternal serum levels of fetal AFP are much
lower but continue to rise until about week 32.

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, decreasing to within it over the first 12 years 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.

References
1. ^ Tomasi TB (1977). "Structure and function of alpha-fetoprotein". Annual review of
medicine 28: 45365. doi:10.1146/annurev.me.28.020177.002321. PMID 67821.
2. ^ Mizejewski GJ (May 2001). "Alpha-fetoprotein structure and function: relevance to
isoforms, epitopes, and conformational variants". Experimental biology and medicine
(Maywood, N.J.) 226 (5): 377408. PMID 11393167.
http://www.ebmonline.org/cgi/content/abstract/226/5/377.
3. ^ Harper ME, Dugaiczyk A (July 1983). "Linkage of the evolutionarily-related serum
albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4". American
journal of human genetics 35 (4): 56572. PMID 6192711.
4. ^ a b "Entrez Gene: Alpha-fetoprotein". http://www.ncbi.nlm.nih.gov/sites/entrez?
Db=gene&Cmd=ShowDetailView&TermToSearch=174.
5. ^ LabCorp 2004 Annual Report
6. ^ Ball D, Rose E, Alpert E (1992). "Alpha-fetoprotein levels in normal adults". Am. J.
Med. Sci. 303 (3): 1579. doi:10.1097/00000441-199203000-00004. PMID 1375809.

7. ^ Sizaret P, Martel N, Tuyns A, Reynaud S (1977). "Mean alpha-fetoprotein values of

1,333 males over 15 years by age groups". Digestion 15 (2): 97103.
doi:10.1159/000197990. PMID 65304.
8. ^ Blohm ME, Vesterling-Hrner D, Calaminus G, Gbel U (1998). "Alpha 1-fetoprotein
(AFP) reference values in infants up to 2 years of age.". Pediatric hematology and
oncology 15 (2): 13542. doi:10.3109/08880019809167228. PMID 9592840.
9. ^ Ohama K, Nagase H, Ogino K, et al. (1997). "Alpha-fetoprotein (AFP) levels in
normal children.". European journal of pediatric surgery : official journal of Austrian
Association of Pediatric Surgery ... [et al.] = Zeitschrift fr Kinderchirurgie 7 (5): 2679.
doi:10.1055/s-2008-1071168. PMID 9402482.
10. ^ a b Lee PI, Chang MH, Chen DS, Lee CY (January 1989). "Serum alpha-fetoprotein
levels in normal infants: a reappraisal of regression analysis and sex difference". J.
Pediatr. Gastroenterol. Nutr. 8 (1): 1925. doi:10.1097/00005176-198901000-00005.
PMID 2471821.
11. ^ Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R (1987). "Plasma alpha
fetoprotein reference ranges in infancy: effect of prematurity.". Arch. Dis. Child. 62 (4):
3629. doi:10.1136/adc.62.4.362. PMID 2439023.
12. ^ Bader D, Riskin A, Vafsi O, et al. (2004). "Alpha-fetoprotein in the early neonatal
period--a large study and review of the literature". Clin. Chim. Acta 349 (1-2): 1523.
doi:10.1016/j.cccn.2004.06.020. PMID 15469851.
13. ^ Wu JT, Roan Y, Knight JA (1985). "Serum levels of AFP in normal infants: their
clinical and physiological significance". In Mizejewski GJ, Porter I. Alfa-Fetoprotein and
Congenital Disorders. Academic Press. pp. 111122.
14. ^ Tim, P, et al.. Hepatoblastoma. http://hepatoblastoma.mditv.com/.
15. ^ Jassam N, Jones CM, Briscoe T, Horner JH (2006). "The hook effect: a need for
constant vigilance.". Ann. Clin. Biochem. 43 (Pt 4): 3147.
doi:10.1258/000456306777695726. PMID 16824284. PubMed
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