Alpha-fetoprotein: Difference between revisions

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{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''Alpha-fetoprotein''' ('''AFP''', '''α-fetoprotein'''; also sometimes called '''alpha-1-fetoprotein''', '''alpha-fetoglobulin''', or '''alpha fetal protein''') is a [[protein]]<ref name="pmid67821">{{cite journal | author = Tomasi TB | title = Structure and function of alpha-fetoprotein | journal = Annual Review of Medicine | volume = 28 | issue = | pages = 453–65 | year = 1977 | pmid = 67821 | doi = 10.1146/annurev.me.28.020177.002321 | url = }}</ref><ref name="pmid11393167">{{cite journal | author = Mizejewski GJ | title = Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants | journal = Experimental Biology and Medicine | volume = 226 | issue = 5 | pages = 377–408 |date=May 2001 | pmid = 11393167 | doi = 10.1177/153537020122600503 | url = http://www.ebmonline.org/cgi/content/abstract/226/5/377 | issn = }}</ref> that in humans is encoded by the ''AFP'' [[gene]].<ref name="pmid6192711">{{cite journal |vauthors=Harper ME, Dugaiczyk A | title = Linkage of the evolutionarily-related serum albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4 | journal = American Journal of Human Genetics | volume = 35 | issue = 4 | pages = 565–72 |date=July 1983 | pmid = 6192711 | pmc = 1685723 | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: Alpha-fetoprotein | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=174| accessdate = }}</ref> The ''AFP'' gene is located on the ''q'' arm of [[chromosome 4]] (4q25).
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Alpha-fetoprotein
| HGNCid = 317
| Symbol = AFP
| AltSymbols =; FETA; HPAFP
| OMIM = 104150
| ECnumber = 
| Homologene = 36278
| MGIid = 87951
| GeneAtlas_image1 = PBB_GE_AFP_204694_at_tn.jpg
| Function = {{GNF_GO|id=GO:0005386 |text = transmembrane transporter activity}} {{GNF_GO|id=GO:0005507 |text = copper ion binding}} {{GNF_GO|id=GO:0016151 |text = nickel ion binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0001542 |text = ovulation (sensu Mammalia)}} {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0019953 |text = sexual reproduction}} {{GNF_GO|id=GO:0042448 |text = progesterone metabolic process}}  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 174
    | Hs_Ensembl = ENSG00000081051
    | Hs_RefseqProtein = NP_001125
    | Hs_RefseqmRNA = NM_001134
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 74520797
    | Hs_GenLoc_end = 74540356
    | Hs_Uniprot = P02771
    | Mm_EntrezGene = 11576
    | Mm_Ensembl = ENSMUSG00000054932
    | Mm_RefseqmRNA = NM_007423
    | Mm_RefseqProtein = NP_031449
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 91565937
    | Mm_GenLoc_end = 91584107
    | Mm_Uniprot = Q3TGA3
  }}
}}


{{DiseaseDisorder infobox |
AFP is a major [[plasma protein]] produced by the [[yolk sac]] and the fetal liver during fetal development. It is thought to be the fetal analog of [[serum albumin]].  AFP [[Organocopper compound|binds to copper]], [[Organonickel|nickel]], [[fatty acid]]s and [[bilirubin]]<ref name="entrez"/> and is found in [[monomer]]ic, [[Protein dimer|dimeric]] and [[Protein trimer|trimeric]] forms.
  Name        = Elevated alphafetoprotein |
  ICD10      = R77.2, Z36.1 |
  ICD9        = {{ICD9|V28.1}} |
}}
{{SI}}
{{CMG}}


==Overview==
== Structure ==
'''Alpha-fetoprotein''' ('''AFP''') is a molecule produced in the developing [[embryo]] and [[fetus]].  In humans, AFP levels decrease gradually after birth, reaching adult levels by 8 to 12 months.  Normal adult AFP levels are low, but detectable;  however, AFP has no known function in normal 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 developmental abnormalities, principally open neural tube defects.  It is also measured in pregnant women, other adults, and children, serving as a biomarker to detect a subset of tumors, principally [[hepatocellular carcinoma]] and [[endodermal sinus tumor]]s.


==Structure and levels==
AFP is a [[glycoprotein]] of 591 amino acids<ref name="pmid1709810">{{cite journal |vauthors=Pucci P, Siciliano R, Malorni A, Marino G, Tecce MF, Ceccarini C, Terrana B | title = Human alpha-fetoprotein primary structure: a mass spectrometric study | journal = Biochemistry | volume = 30 | issue = 20 | pages = 5061–6 |date=May 1991 | pmid = 1709810 | doi = 10.1021/bi00234a032| url = }}</ref> and a carbohydrate moiety.<ref name="pmid7544570">{{cite journal |vauthors=Seregni E, Botti C, Bombardieri E | title = Biochemical characteristics and clinical applications of alpha-fetoprotein isoforms | journal = Anticancer Res. | volume = 15 | issue = 4 | pages = 1491–9 | year = 1995 | pmid = 7544570 | doi =  }}</ref>
AFP is a [[glycoprotein]] of 590 amino acids and a carbohydrate moiety. Many functions have been proposed for AFP; 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 sac|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==
== Function ==
LabCorp, a large [[United States|US]] clinical laboratory testing company, began offering AFP screening tests in the early 1980s.<ref>[http://www.labcorp.com/2004_annual_report/LabCorp_AR2004_1.pdf LabCorp 2004 Annual Report]</ref>
AFP is the most abundant plasma protein found in the human fetus. Maternal plasma levels peak near the end of the first trimester, and begin decreasing prenatally at that time, then decrease rapidly after birth. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adult humans is unknown; however, in rodents it binds [[estradiol]] to prevent the transport of this hormone across the [[placenta]] to the fetus. The main function of this is to prevent the [[virilization]] of female fetuses. As human AFP does not bind estrogen, its function in humans is less clear.<ref name="isbn0-262-52321-3">{{cite book | editor = Becker JB  | title = Behavioral Endocrinology | chapter = Neuroendocrinology of sexual behavior in the female | author = Carter CS | publisher = MIT Press | location = Cambridge, Massachusetts | year = 2002  | pages = 88–89  | isbn = 0-262-52321-3 | url = https://books.google.com/books?id=D6TnKbTRBJoC&lpg=PA88&ots=jgmtzhDR8p&dq=AFP%20binds%20maternal%20estrogen&pg=PA88#v=onepage&q=AFP%20binds%20maternal%20estrogen&f=false }}</ref>


==AFP in normal infants==
The rodent AFP system can be overridden with massive injections of estrogen, which overwhelm the AFP system and will masculinize the fetus. The masculinizing effect of estrogens may seem counter-intuitive since estrogens are critical for the proper development of female secondary characteristics during puberty. However, this is not the case prenatally. Gonadal hormones from the testes, such as [[testosterone]] and [[antimullerian hormone]] are required to cause development of a phenotypic male. Without these hormones the fetus will develop into a phenotypic female even if genetically [[XY sex-determination system|XY]]. The conversion of testosterone into estradiol by [[aromatase]] in many tissues may be an important step in masculinization of that tissue.<ref name="pmid11124800">{{cite journal |vauthors=Nef S, Parada LF | title = Hormones in male sexual development | journal = Genes Dev. | volume = 14 | issue = 24 | pages = 3075–86 |date=December 2000 | pmid = 11124800 | doi = 10.1101/gad.843800 }}</ref><ref name="pmid1734525">{{cite journal|vauthors=Elbrecht A, Smith RG | title=Aromatase enzyme activity and sex determination in chickens. | journal=Science | year= 1992 | volume= 255 | issue= 5043 | pages= 467–70 | pmid=1734525 | doi= 10.1126/science.1734525}}</ref> Masculinization of the brain is thought to occur both by conversion of testosterone into estradiol by aromatase, but also by [[de novo synthesis]] of estrogens within the brain.<ref name="pmid17720235">{{cite journal|vauthors=Bakker J, Baum MJ | title=Role for estradiol in female-typical brain and behavioral sexual differentiation. | journal=Front Neuroendocrinol | year= 2008 | volume= 29 | issue= 1 | pages= 1–16 | pmid=17720235 | doi=10.1016/j.yfrne.2007.06.001 | pmc= 2373265 }}</ref><ref name="pmid15313793">{{cite journal| author=Harding CF| title=Hormonal modulation of singing: hormonal modulation of the songbird brain and singing behavior. | journal=Annals of the New York Academy of Sciences | year= 2004 | volume= 1016 | issue=  | pages= 524–39 | pmid=15313793 | doi=10.1196/annals.1298.030 }}</ref> Thus, AFP may protect the fetus from maternal estradiol that would otherwise have a masculinizing effect on the fetus, but its exact role is still controversial.
The normal range of AFP for adults is variously reported as under 50, under 10, and under 5. At birth, normal infants have AFP levels 4 or more magnitudes above<ref name="pmid9592840">{{cite journal
| author = Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U
| title = Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age.
| journal = Pediatric hematology and oncology
| volume = 15
| issue = 2
| pages = 135-42
| year = 1998
| pmid = 9592840
| doi =
| issn =
}}</ref><ref name="pmid9402482">{{cite journal
| author = Ohama K, Nagase H, Ogino K, ''et al''
| title = Alpha-fetoprotein (AFP) levels in normal children.
| journal = European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift für Kinderchirurgie
| volume = 7
| issue = 5
| pages = 267-9
| year = 1997
| pmid = 9402482
| doi =
| issn =
}}</ref><ref name="pmid2483492">{{cite journal
| author = Lee PI, Chang MH, Chen DS, Lee CY
| title = Serum alpha-fetoprotein in normal Chinese infants.
| journal = Zhonghua Minguo xiao er ke yi xue hui za zhi [Journal]. Zhonghua Minguo xiao er ke yi xue hui
| volume = 29
| issue = 3
| pages = 152-8
| year = 1988
| pmid = 2483492
| doi =  
| issn =
}}</ref><ref name="pmid2439023">{{cite journal
| author = Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R
| title = Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity.
| journal = Arch. Dis. Child.
| volume = 62
| issue = 4
| pages = 362-9
| year = 1987
| pmid = 2439023
| doi =  
| issn =
}}</ref><ref name="pmid15469851">{{cite journal
| author = Bader D, Riskin A, Vafsi O, ''et al''
| title = Alpha-fetoprotein in the early neonatal period--a large study and review of the literature
| journal = Clin. Chim. Acta
| volume = 349
| issue = 1-2
| pages = 15-23
| year = 2004
| pmid = 15469851
| doi = 10.1016/j.cccn.2004.06.020
| issn =  
}}</ref><ref name="Wu+1985">{{cite book
| author = Wu JT, Roan Y, Knight JA
| chapter = Serum levels of AFP in normal infants: their clinical and physiological significance
| title = Alfa-Fetoprotein and Congenital Disorders
| editor = Mizejewski GJ, Porter I
| year = 1985
  | pages = 111-122
| publisher = Academic Press
| address = New York
}}</ref> the normal range for adults,<ref name="pmid1375809">{{cite journal
| author = Ball D, Rose E, Alpert E
| title = Alpha-fetoprotein levels in normal adults
| journal = Am. J. Med. Sci.
| volume = 303
| issue = 3
| pages = 157-9
| year = 1992
| pmid = 1375809
| doi =
| issn =


| doi = 10.1097/00000441-199203000-00004
== Serum levels ==
}}</ref><ref name="pmid65304">{{cite journal
{{main|Elevated alpha-fetoprotein}}
| author = Sizaret P, Martel N, Tuyns A, Reynaud S
| title = Mean alpha-fetoprotein values of 1,333 males over 15 years by age groups
| journal = Digestion
| volume = 15
| issue = 2
| pages = 97-103
| year = 1977
| pmid = 65304
| doi =
| issn =
}}</ref> decreasing to adult levels over the first year of life.  Correct evaluation of ''abnormal'' AFP levels in infants must take into account this normal pattern.


Very high AFP levels may be subject to [[tumor marker|'''hooking''']], resulting in a false low level.<ref name="Jassam+2006">{{cite journal
=== Maternal ===
| author = Jassam N, Jones CM, Briscoe T, Horner JH
| title = The hook effect: a need for constant vigilance.
| journal = Ann. Clin. Biochem.
| volume = 43
| issue = Pt 4
| pages = 314-7
| year = 2006
| pmid = 16824284
| doi = 10.1258/000456306777695726
| issn =
}} {{PMID|16824284}}</ref>


In pregnant women, fetal AFP levels can be monitored in urine. Since AFP is quickly cleared from the mother's serum via her kidneys, maternal urine AFP correlates with fetal serum levels, although the maternal urine level is much lower than the fetal serum level. AFP levels rise until about week 32.


==AFP tests==
=== Infants ===
There are two categories of AFP tests:  tests performed on [[blood plasma|serum (blood plasma)]], and tests performed on
[[amniotic sac|amniotic fluid]].  Tests performed on serum are further categorized by the reason for performing the test:  maternal serum, adult tumor marker, and pediatric tumor marker.


===Tests performed on [[blood plasma|serum]]===
The normal range of AFP for adults and children is variously reported as under 50, under 10, and under 5&nbsp;ng/mL.<ref name="pmid1375809">{{cite journal |vauthors=Ball D, Rose E, Alpert E | title = Alpha-fetoprotein levels in normal adults | journal = Am. J. Med. Sci. | volume = 303 | issue = 3 | pages = 157–9 |date=March 1992 | pmid = 1375809 | doi = 10.1097/00000441-199203000-00004  }}</ref><ref name="pmid65304">{{cite journal |vauthors=Sizaret P, Martel N, Tuyns A, Reynaud S | title = Mean alpha-fetoprotein values of 1,333 males over 15 years by age groups | journal = Digestion | volume = 15 | issue = 2 | pages = 97–103 |date=February 1977 | pmid = 65304 | doi = 10.1159/000197990 }}</ref> At birth, normal infants have AFP levels 4 or more [[Order of magnitude|orders of magnitude]] above this normal range, that decreases to a normal range over the first year of life.<ref name="pmid9592840">{{cite journal |vauthors=Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U | title = Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age | journal = Pediatr Hematol Oncol | volume = 15 | issue = 2 | pages = 135–42 | year = 1998 | pmid = 9592840 | doi = 10.3109/08880019809167228 }}</ref><ref name="pmid9402482">{{cite journal |vauthors=Ohama K, Nagase H, Ogino K, Tsuchida K, Tanaka M, Kubo M, Horita S, Kawakami K, Ohmori M | title = Alpha-fetoprotein (AFP) levels in normal children | journal = Eur J Pediatr Surg | volume = 7 | issue = 5 | pages = 267–9 |date=October 1997 | pmid = 9402482 | doi = 10.1055/s-2008-1071168 }}</ref><ref name="pmid2471821">{{cite journal |vauthors=Lee PI, Chang MH, Chen DS, Lee CY | title = Serum alpha-fetoprotein levels in normal infants: a reappraisal of regression analysis and sex difference | journal = J. Pediatr. Gastroenterol. Nutr. | volume = 8 | issue = 1 | pages = 19–25 |date=January 1989 | pmid = 2471821 | doi = 10.1097/00005176-198901000-00005 }}</ref><ref name="pmid2439023">{{cite journal |vauthors=Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R | title = Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity | journal = Arch. Dis. Child. | volume = 62 | issue = 4 | pages = 362–9 |date=April 1987 | pmid = 2439023 | pmc = 1778344 | doi = 10.1136/adc.62.4.362 }}</ref><ref name="pmid15469851">{{cite journal |vauthors=Bader D, Riskin A, Vafsi O, Tamir A, Peskin B, Israel N, Merksamer R, Dar H, David M | title = Alpha-fetoprotein in the early neonatal period--a large study and review of the literature | journal = Clin. Chim. Acta | volume = 349 | issue = 1-2 | pages = 15–23 |date=November 2004 | pmid = 15469851 | doi = 10.1016/j.cccn.2004.06.020 }}</ref><ref name="Wu+1985">{{cite book |vauthors=Wu JT, Roan Y, Knight JA | chapter = Serum levels of AFP in normal infants: their clinical and physiological significance | title = Alfa-Fetoprotein and Congenital Disorders |veditors=Mizejewski GJ, Porter I | year = 1985 | pages = 111–122 | publisher = Academic Press | location = New York }}</ref>
The standard is a quantitative test, reporting a measured concentration of AFP in the sample, but there is also a less expensive qualitative test, reporting only that the concentration is normal or high. The qualitative test is appropriate only in some circumstances.


The resulting test report should specify the assay method and equipment used, and the report of a quantitative test should also provide a reference range for the test result.  Many laboratories report reference ranges that are based on all other samples tested in that laboratory, necessarily including samples with abnormal AFP concentrations due to disease.  Superior reference ranges are produced by research on healthy subjects.
During this time, the normal range of AFP levels spans approximately 2 orders of magnitude.<ref name="pmid2471821"/> Correct evaluation of ''abnormal'' AFP levels in infants must take into account these normal patterns.<ref name="pmid2471821"/>


====Maternal serum====
Very high AFP levels may be subject to '''hooking''' (see [[Tumor marker]]), which results in the level being reported significantly lower than the actual concentration.<ref name="pmid16824284">{{cite journal |vauthors=Jassam N, Jones CM, Briscoe T, Horner JH | title = The hook effect: a need for constant vigilance | journal = Ann. Clin. Biochem. | volume = 43 | issue = Pt 4 | pages = 314–7 |date=July 2006 | pmid = 16824284 | doi = 10.1258/000456306777695726 }}</ref>  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.
[[Maternal]] serum AFP tests need to be interpreted according to the gestational age, as levels rise until about 32 weeks gestation. Typically, such measurements are done in the middle of the second trimester (14-16 weeks). Elevated levels are seen in [[multiple birth|multiple gestation]] as well as in a number of fetal abnormalities, such as [[neural tube defect]]s including [[spina bifida]] and [[anencephaly]], and [[abdominal wall defect]]s. Other possibilities are errors in the date of the gestation or fetal demise. In contrast, low levels of maternal serum AFP are associated with [[Down syndrome]] and [[Trisomy 18]]. Diabetic patients also have lower levels. Patients with abnormal levels need to undergo detailed [[obstetric ultrasonography]]. The information is then used to decide whether to proceed with [[amniocentesis]].


Maternal serum AFP may be measured as part of a routine prenatal screening test:
== Clinical significance ==
* [[Triple test]]: AFP, [[Human chorionic gonadotropin|hCG]] and [[estriol]]
{{main|Elevated alpha-fetoprotein}}
* '''Quad test''': AFP, [[Human chorionic gonadotropin|hCG]], [[estriol]], and [[Inhibin]]
Measurement of AFP is generally used in two clinical contexts. First, it is measured in pregnant women through the analysis of maternal [[blood]] or [[amniotic fluid]] as a screening test for certain developmental abnormalities such as [[aneuploidy]].  Second, serum AFP level is elevated in people with certain tumors, and so it is used as a [[biomarker]] to follow these diseases. Some of these diseases are listed below:
* [[Genetic counseling]] usually is offered when the screening test result is positive.
* ''Developmental birth defects associated with elevated AFP''
**[[Omphalocele]]<ref name="pmid1699194">{{cite journal |vauthors=Szabó M, Veress L, Münnich A, Papp Z | title = [Alpha fetoprotein concentration in the amniotic fluid in normal pregnancy and in pregnancy complicated by fetal anomaly] | language = Hungarian | journal = Orv Hetil | volume = 131 | issue = 39 | pages = 2139–42 |date=September 1990 | pmid = 1699194 | doi =  }}</ref><ref name="pmid16533649">{{cite journal |vauthors=Rosen T, D'Alton ME | title = Down syndrome screening in the first and second trimesters: what do the data show? | journal = Semin. Perinatol. | volume = 29 | issue = 6 | pages = 367–75 |date=December 2005 | pmid = 16533649 | doi = 10.1053/j.semperi.2006.01.001 }}</ref>
**[[Gastroschisis]]
** [[Neural tube defect]]s: ↑ α-fetoprotein in amniotic fluid and maternal serum<ref name="Tao p 1" /><ref name="pmid22377693">{{cite journal|year=2012|title=First-trimester screening for neural tube defects using alpha-fetoprotein|journal=Fetal Diagn. Ther.|volume=31|issue=2|pages=109–14|doi=10.1159/000335677|pmid=22377693|vauthors=Bredaki FE, Poon LC, Birdir C, Escalante D, Nicolaides KH}}</ref>
* ''Tumors associated with elevated AFP''
** [[Hepatocellular carcinoma]]<ref name="Tao p 1">Le, Tao. First Aid for the USMLE Step 1 2013. New York: McGraw-Hill Medical, 2013. Print.</ref><ref>{{cite journal|last1=Ertle|first1=JM|last2=Heider|first2=D|last3=Wichert|first3=M|last4=Keller|first4=B|last5=Kueper|first5=R|last6=Hilgard|first6=P|last7=Gerken|first7=G|last8=Schlaak|first8=JF|title=A combination of α-fetoprotein and des-γ-carboxy prothrombin is superior in detection of hepatocellular carcinoma.|journal=Digestion|date=2013|volume=87|issue=2|pages=121–31|pmid=23406785|doi=10.1159/000346080}}</ref>
** Metastatic disease affecting the liver
** Nonseminomatous [[germ cell tumor]]s
** [[Yolk sac tumor]]<ref name="Tao p 1" />
* ''Other conditions associated with elevated AFP''
** [[Ataxia-telangiectasia|Ataxia telangiectasia]]: elevated AFP is used as one factor in diagnosis<ref name="pmid16189143">{{cite journal |vauthors=Taylor AM, Byrd PJ | title = Molecular pathology of ataxia telangiectasia | journal = J. Clin. Pathol. | volume = 58 | issue = 10 | pages = 1009–15 |date=October 2005 | pmid = 16189143 | pmc = 1770730 | doi = 10.1136/jcp.2005.026062 }}</ref>


====Tumor marker====
A peptide derived from AFP that is referred to as [[AFPep]] is claimed to possess anti-cancer properties.<ref name="pmid10727847">{{cite journal |vauthors=Mesfin FB, Bennett JA, Jacobson HI, Zhu S, Andersen TT | title = Alpha-fetoprotein-derived antiestrotrophic octapeptide | journal = Biochimica et Biophysica Acta | volume = 1501 | issue = 1 | pages = 33–43 |date=April 2000 | pmid = 10727847 | doi = 10.1016/S0925-4439(00)00008-9 }}</ref>
Like any elevated [[tumor marker]], elevated AFP by itself is not diagnostic, only suggestive. Tumor markers are used primarily to monitor the result of a treatment (e.g. [[chemotherapy]]). If levels of AFP go down after treatment, the tumor is not growing.  In the case of babies, after treatment AFP should go down '''faster''' than it would normally. A temporary increase in AFP immediately following chemotherapy may indicate not that the tumor is growing but rather that it is shrinking (and releasing AFP as the tumor cells die).  [[AFP-L3]], an isoform of AFP which binds [[Lentil|''Lens culinaris'']] agglutinin, can be particularly useful in early identification of aggressive tumors associated with [[hepatocellular carcinoma]] (HCC).


AFP is the main [[tumor marker]] (sometimes with [[Human chorionic gonadotropin|HCG]]) used to monitor [[testicular cancer]], [[ovarian cancer]], and [[teratoma|malignant teratoma]] in any location:  values of AFP over time can have significant effect on the treatment plan.
==See also==
 
*[[Tumor marker]]
AFP is normally elevated in infants, and because [[teratoma]] is the single most common kind of tumor in infants, several studies have provided reference ranges for AFP in normal infants.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=6163129 Serum alpha fetoprotein (AFP) levels in normal infants]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=9592840 Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15469851 Alpha-fetoprotein in the early neonatal period--a large study and review of the literature]</ref>.  Perhaps the most useful is this equation:  log Y = 7.397 - 2.622.log (X + 10), where X = age in days and Y = AFP level in nanograms per milliliter.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=2471821 Serum alpha-fetoprotein levels in normal infants: a reappraisal of regression analysis and sex difference]</ref>
*[[AFP-L3]]
 
*[[Triple test]]
<!-- === Tests performed on [[amniotic sac|amniotic fluid]]===
*[[Advanced maternal age]]
-->
*[[AFP and AFP non-covalent complex as a drug]]
 
=== Tests performed on [[cerebrospinal fluid]] (CSF) ===
In normal infants, AFP in CSF is<ref>Coakley J, Kellie SJ, Nath C, Munas A, Cooke-Yarborough C. Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants. Ann Clin Biochem. 2005 Jan;42(Pt 1):24-9. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15802029 PubMed abstract]</ref>:
* median 61 kIU/L (5th-95th centile: 2-889 kIU/L) in infants -69 to 31 days old
* median 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L) in infants 32 to 110 days old
Levels of AFP in CSF decline with gestational age in proportion to levels of AFP in serum<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=10612715 Alpha-fetoprotein in human fetal cerebrospinal fluid]</ref>
 
==Interpretation of AFP test results==
 
AFP test results often are reported as either ng/ml or MoM ([[multiple of the median]], where the median is calculated for an appropriate reference population).
 
===Maternal serum===
Abnormally elevated AFP in the serum of a pregnant woman can have one or more of these sources:
 
* a problem with the fetus
* a problem with the placenta
* a [[tumor]] or [[liver]] disease in the woman
* a normally elevated AFP in the fetus or woman (some people naturally have very high AFP)
 
Usual follow-up steps include (1) a [[prenatal ultrasound]] exam to look for fetal abnormalities and/or (2) measurement of AFP in amniotic fluid obtained via [[amniocentesis]].
 
===Amniotic fluid===
AFP in amniotic fluid has one or two sources.  The fetus normally excretes AFP into its urine, hence into the amniotic fluid.  A fetus with one of three broad categories of defects also releases AFP by other means.  These categories are '''open''' [[neural tube defect]], '''open''' [[abdominal wall defect]], and [[skin disease]] or other failure of the interior or exterior body surface.
 
Abnormally elevated AFP in amniotic fluid can have one or more of many different causes:
 
* normal elevation.  75% of AF AFP test results in the range 2.0 to 4.9 [[MoM]] are false positives:  the baby is normal.
* open neural tube defect
* open abdominal wall defect
* [[congenital nephrosis]]
* others
 
==Sources of AFP:  Normal==
 
Serum alpha-fetoprotein is a fetal serum protein produced by the yolk sac and liver.
 
==Sources of AFP:  Abnormal==
 
===Tumors===
 
Principal [[tumor]]s that secrete AFP are [[endodermal sinus tumor]] (yolk sac carcinoma), [[neuroblastoma]], [[hepatoblastoma]], and [[hepatocellular carcinoma]].
 
With regard to hepatocellular carcinoma, AFP is not useful for screening<ref name="pmid18087192">{{cite journal
| author = Paul SB, Gulati MS, Sreenivas V, Madan K, Gupta AK, Mukhopadhyay S, Acharya SK
| title = Evaluating patients with cirrhosis for hepatocellular carcinoma: value of clinical symptomatology, imaging and alpha-fetoprotein.
| journal = Oncology
| volume = 72 Suppl 1
| issue =
| pages = 117–23
| year = 2007
| pmid = 18087192
| doi = 10.1159/000111717
| issn =
}}</ref> but is somewhat useful for surveillance after treatment.<ref name="pmid18087182">{{cite journal
| author = Kim do Y, Paik YH, Ahn SH, Youn YJ, Choi JW, Kim JK, Lee KS, Chon CY, Han KH
| title = PIVKA-II is a useful tumor marker for recurrent hepatocellular carcinoma after surgical resection.
| journal = Oncology
| volume = 72 Suppl 1
| issue =
| pages = 52–7
| year = 2007
| pmid = 18087182
| doi = 10.1159/000111707
| issn =
}}</ref>
 
Rare AFP-secreting tumor types include [[carcinoma]] in a [[malignant mixed Müllerian tumor]].<ref name="pmid10739713">{{cite journal
| author = Rebischung C, Pautier P, Morice P, Lhomme C, Duvillard P
| title = Alpha-fetoprotein production by a malignant mixed Müllerian tumor of the ovary.
| journal = Gynecol. Oncol.
| volume = 77
| issue = 1
| pages = 203–5
| year = 2000
| pmid = 10739713
| doi = 10.1006/gyno.1999.5653
| issn =
}}</ref>
 
In [[Wilms tumor]] AFP is rarely elevated, but when it is elevated it may serve as a marker of disease progression or recurrence.<ref name="pmid17987303">{{cite journal
| author = Crocoli A, Madafferi S, Jenkner A, Zaccara A, Inserra A
| title = Elevated serum alpha-fetoprotein in Wilms tumor may follow the same pattern of other fetal neoplasms after treatment: evidence from three cases.
| journal = Pediatr Surg Int
| volume =
| issue =
| pages =
| year = 2007
| pmid = 17987303
| doi = 10.1007/s00383-007-2067-7
| issn =
 
| pages = 499
}}</ref>
 
There are [[case report]]s of elevated AFP associated with [[teratoma]].  However, some of these case reports involve [[infant]]s but do not correct for the normal elevation of AFP in infants, while others ignore the likelihood that teratoma (and other [[germ cell tumor]]s) may in fact be mixed tumors containing elements of endodermal sinus tumor.
 
In patients with AFP-secreting tumors, serum levels of AFP often correlate with tumor size. Resection is usually associated with a fall in serum levels. Serum levels are useful in assessing response to treatment.
 
===Other===
Increased serum levels in adults are also seen in acute hepatitis, colitis and ataxia telangiectasia.


==References==
==References==
{{reflist|2}}
{{reflist|30em}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|colwidth=35em}}
{{PBB_Further_reading
*{{cite journal  | author=Nahon JL |title=The regulation of albumin and alpha-fetoprotein gene expression in mammals |journal=Biochimie |volume=69 |issue= 5 |pages= 445–59 |year= 1987 |pmid= 2445387 |doi=  10.1016/0300-9084(87)90082-4}}
| citations =
*{{cite journal  | author=Tilghman SM |title=The structure and regulation of the alpha-fetoprotein and albumin genes |journal=Oxf. Surv. Eukaryot. Genes |volume=2 |issue=  |pages= 160–206 |year= 1989 |pmid= 2474300 |doi=  }}
*{{cite journal  | author=Nahon JL |title=The regulation of albumin and alpha-fetoprotein gene expression in mammals. |journal=Biochimie |volume=69 |issue= 5 |pages= 445-59 |year= 1987 |pmid= 2445387 |doi=  }}
*{{cite journal  | author=Mizejewski GJ |title=Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy |journal=Expert Rev Anticancer Ther |volume=2 |issue= 6 |pages= 709–35 |year= 2003 |pmid= 12503217 |doi= 10.1586/14737140.2.6.709 }}
*{{cite journal  | author=Tilghman SM |title=The structure and regulation of the alpha-fetoprotein and albumin genes. |journal=Oxf. Surv. Eukaryot. Genes |volume=2 |issue=  |pages= 160-206 |year= 1989 |pmid= 2474300 |doi=  }}
*{{cite journal  |vauthors=Yachnin S, Hsu R, Heinrikson RL, Miller JB |title=Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis |journal=Biochim. Biophys. Acta |volume=493 |issue= 2 |pages= 418–28 |year= 1977 |pmid= 70228 |doi= 10.1016/0005-2795(77)90198-2 }}
*{{cite journal  | author=Mizejewski GJ |title=Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy. |journal=Expert Rev Anticancer Ther |volume=2 |issue= 6 |pages= 709-35 |year= 2003 |pmid= 12503217 |doi= 10.1586/14737140.2.6.709 }}
*{{cite journal  |vauthors=Aoyagi Y, Ikenaka T, Ichida F |title=Comparative chemical structures of human alpha-fetoproteins from fetal serum and from ascites fluid of a patient with hepatoma |journal=Cancer Res. |volume=37 |issue= 10 |pages= 3663–7 |year= 1977 |pmid= 71198 |doi=  }}
*{{cite journal  | author=Yachnin S, Hsu R, Heinrikson RL, Miller JB |title=Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis. |journal=Biochim. Biophys. Acta |volume=493 |issue= 2 |pages= 418-28 |year= 1977 |pmid= 70228 |doi= }}
*{{cite journal  |vauthors=Aoyagi Y, Ikenaka T, Ichida F |title=Copper(II)-binding ability of human alpha-fetoprotein |journal=Cancer Res. |volume=38 |issue= 10 |pages= 3483–6 |year= 1978 |pmid= 80265 |doi=  }}
*{{cite journal  | author=Aoyagi Y, Ikenaka T, Ichida F |title=Comparative chemical structures of human alpha-fetoproteins from fetal serum and from ascites fluid of a patient with hepatoma. |journal=Cancer Res. |volume=37 |issue= 10 |pages= 3663-7 |year= 1977 |pmid= 71198 |doi=  }}
*{{cite journal  |vauthors=Aoyagi Y, Ikenaka T, Ichida F |title=alpha-Fetoprotein as a carrier protein in plasma and its bilirubin-binding ability |journal=Cancer Res. |volume=39 |issue= 9 |pages= 3571–4 |year= 1979 |pmid= 89900 |doi=  }}
*{{cite journal  | author=Aoyagi Y, Ikenaka T, Ichida F |title=Copper(II)-binding ability of human alpha-fetoprotein. |journal=Cancer Res. |volume=38 |issue= 10 |pages= 3483-6 |year= 1978 |pmid= 80265 |doi=  }}
*{{cite journal  |vauthors=Torres JM, Anel A, Uriel J |title=Alpha-fetoprotein-mediated uptake of fatty acids by human T lymphocytes |journal=J. Cell. Physiol. |volume=150 |issue= 3 |pages= 456–62 |year= 1992 |pmid= 1371512 |doi= 10.1002/jcp.1041500305 }}
*{{cite journal  | author=Aoyagi Y, Ikenaka T, Ichida F |title=alpha-Fetoprotein as a carrier protein in plasma and its bilirubin-binding ability. |journal=Cancer Res. |volume=39 |issue= 9 |pages= 3571-4 |year= 1979 |pmid= 89900 |doi=  }}
*{{cite journal  |vauthors=Greenberg F, Faucett A, Rose E |title=Congenital deficiency of alpha-fetoprotein |journal=Am. J. Obstet. Gynecol. |volume=167 |issue= 2 |pages= 509–11 |year= 1992 |pmid= 1379776 |doi=  |display-authors=etal}}
*{{cite journal  | author=Torres JM, Anel A, Uriel J |title=Alpha-fetoprotein-mediated uptake of fatty acids by human T lymphocytes. |journal=J. Cell. Physiol. |volume=150 |issue= 3 |pages= 456-62 |year= 1992 |pmid= 1371512 |doi= 10.1002/jcp.1041500305 }}
*{{cite journal  |vauthors=Bansal V, Kumari K, Dixit A, Sahib MK |title=Interaction of human alpha fetoprotein with bilirubin |journal=Indian J. Exp. Biol. |volume=28 |issue= 7 |pages= 697–8 |year= 1991 |pmid= 1703124 |doi=  }}
*{{cite journal  | author=Greenberg F, Faucett A, Rose E, ''et al.'' |title=Congenital deficiency of alpha-fetoprotein. |journal=Am. J. Obstet. Gynecol. |volume=167 |issue= 2 |pages= 509-11 |year= 1992 |pmid= 1379776 |doi=  }}
*{{cite journal  |vauthors=Pucci P, Siciliano R, Malorni A |title=Human alpha-fetoprotein primary structure: a mass spectrometric study |journal=Biochemistry |volume=30 |issue= 20 |pages= 5061–6 |year= 1991 |pmid= 1709810| doi=10.1021/bi00234a032|display-authors=etal}}
*{{cite journal  | author=Bansal V, Kumari K, Dixit A, Sahib MK |title=Interaction of human alpha fetoprotein with bilirubin. |journal=Indian J. Exp. Biol. |volume=28 |issue= 7 |pages= 697-8 |year= 1991 |pmid= 1703124 |doi=  }}
*{{cite journal  |vauthors=Liu MC, Yu S, Sy J |title=Tyrosine sulfation of proteins from the human hepatoma cell line HepG2 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=82 |issue= 21 |pages= 7160–4 |year= 1985 |pmid= 2414772| doi=10.1073/pnas.82.21.7160 | pmc=390808|display-authors=etal}}
*{{cite journal  | author=Pucci P, Siciliano R, Malorni A, ''et al.'' |title=Human alpha-fetoprotein primary structure: a mass spectrometric study. |journal=Biochemistry |volume=30 |issue= 20 |pages= 5061-6 |year= 1991 |pmid= 1709810 |doi=    | doi=10.1021/bi00234a032}}
*{{cite journal  |vauthors=Gibbs PE, Zielinski R, Boyd C, Dugaiczyk A |title=Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene |journal=Biochemistry |volume=26 |issue= 5 |pages= 1332–43 |year= 1987 |pmid= 2436661| doi=10.1021/bi00379a020}}
*{{cite journal  | author=Liu MC, Yu S, Sy J, ''et al.'' |title=Tyrosine sulfation of proteins from the human hepatoma cell line HepG2. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 21 |pages= 7160-4 |year= 1985 |pmid= 2414772 |doi=    | doi=10.1073/pnas.82.21.7160}}
*{{cite journal  |vauthors=Sakai M, Morinaga T, Urano Y |title=The human alpha-fetoprotein gene. Sequence organization and the 5' flanking region |journal=J. Biol. Chem. |volume=260 |issue= 8 |pages= 5055–60 |year= 1985 |pmid= 2580830 |doi=  |display-authors=etal}}
*{{cite journal  | author=Gibbs PE, Zielinski R, Boyd C, Dugaiczyk A |title=Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene. |journal=Biochemistry |volume=26 |issue= 5 |pages= 1332-43 |year= 1987 |pmid= 2436661 |doi=    | doi=10.1021/bi00379a020}}
*{{cite journal  |vauthors=Ruoslahti E, Pihko H, Vaheri A |title=Alpha fetoprotein: structure and expression in man and inbred mouse strains under normal conditions and liver injury |journal=Johns Hopkins Med. J. Suppl. |volume=3 |issue=  |pages= 249–55 |year= 1975 |pmid= 4138095 |doi=  |display-authors=etal}}
*{{cite journal  | author=Sakai M, Morinaga T, Urano Y, ''et al.'' |title=The human alpha-fetoprotein gene. Sequence organization and the 5' flanking region. |journal=J. Biol. Chem. |volume=260 |issue= 8 |pages= 5055-60 |year= 1985 |pmid= 2580830 |doi=  }}
*{{cite journal  |vauthors=Urano Y, Sakai M, Watanabe K, Tamaoki T |title=Tandem arrangement of the albumin and alpha-fetoprotein genes in the human genome |journal=Gene |volume=32 |issue= 3 |pages= 255–61 |year= 1985 |pmid= 6085063 |doi=10.1016/0378-1119(84)90001-5 }}
*{{cite journal  | author=Ruoslahti E, Pihko H, Vaheri A, ''et al.'' |title=Alpha fetoprotein: structure and expression in man and inbred mouse strains under normal conditions and liver injury. |journal=Johns Hopkins Med. J. Suppl. |volume=3 |issue=  |pages= 249-55 |year= 1975 |pmid= 4138095 |doi=  }}
*{{cite journal  |vauthors=Beattie WG, Dugaiczyk A |title=Structure and evolution of human alpha-fetoprotein deduced from partial sequence of cloned cDNA |journal=Gene |volume=20 |issue= 3 |pages= 415–22 |year= 1983 |pmid= 6187626 |doi=10.1016/0378-1119(82)90210-4 }}
*{{cite journal  | author=Urano Y, Sakai M, Watanabe K, Tamaoki T |title=Tandem arrangement of the albumin and alpha-fetoprotein genes in the human genome. |journal=Gene |volume=32 |issue= 3 |pages= 255-61 |year= 1985 |pmid= 6085063 |doi=  }}
*{{cite journal  |vauthors=Morinaga T, Sakai M, Wegmann TG, Tamaoki T |title=Primary structures of human alpha-fetoprotein and its mRNA |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=80 |issue= 15 |pages= 4604–8 |year= 1983 |pmid= 6192439| doi=10.1073/pnas.80.15.4604 | pmc=384092}}
*{{cite journal  | author=Beattie WG, Dugaiczyk A |title=Structure and evolution of human alpha-fetoprotein deduced from partial sequence of cloned cDNA. |journal=Gene |volume=20 |issue= 3 |pages= 415-22 |year= 1983 |pmid= 6187626 |doi=  }}
*{{cite journal  | author=Morinaga T, Sakai M, Wegmann TG, Tamaoki T |title=Primary structures of human alpha-fetoprotein and its mRNA. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 15 |pages= 4604-8 |year= 1983 |pmid= 6192439 |doi=    | doi=10.1073/pnas.80.15.4604}}
}}
{{refend}}
{{refend}}


==See also==
==External links==
*[[Tumor marker]]
* {{MeshName|alpha-Fetoproteins}}
*[[AFP-L3]]
 


{{Tumor markers}}
{{Tumor markers}}
{{NLM content}}


[[Category:Glycoproteins]]
[[Category:Glycoproteins]]
[[Category:Tumor markers]]
[[Category:Tumor markers]]
[[Category:Obstetrics]]
[[Category:Obstetrics]]
[[Category:Laboratory Test]]
[[Category:Midwifery]]
 
[[de:Alpha-1-Fetoprotein]]
[[es:Alfa-fetoproteína]]
[[fr:Alpha-fœtoprotéine]]
[[it:Alfa-feto proteina]]
[[ja:Α-フェトプロテイン]]
[[pl:Αlfa-fetoproteina]]
[[pt:Alfa feto proteína]]
[[ru:Альфа-фетопротеин]]
[[fi:Alfa-fetoproteiini]]
[[zh:Α-胎兒蛋白]]
 
{{WH}}
{{WS}}

Latest revision as of 15:08, 15 January 2019

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View/Edit Human

Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein[1][2] that in humans is encoded by the AFP gene.[3][4] The AFP gene is located on the q arm of chromosome 4 (4q25).

AFP is a major plasma protein produced by the yolk sac and the fetal liver during fetal development. It is thought to be the fetal analog of serum albumin. AFP binds to copper, nickel, fatty acids and bilirubin[4] and is found in monomeric, dimeric and trimeric forms.

Structure

AFP is a glycoprotein of 591 amino acids[5] and a carbohydrate moiety.[6]

Function

AFP is the most abundant plasma protein found in the human fetus. Maternal plasma levels peak near the end of the first trimester, and begin decreasing prenatally at that time, then decrease rapidly after birth. Normal adult levels are usually achieved by the age of 8 to 12 months. The function of AFP in adult humans is unknown; however, in rodents it binds estradiol to prevent the transport of this hormone across the placenta to the fetus. The main function of this is to prevent the virilization of female fetuses. As human AFP does not bind estrogen, its function in humans is less clear.[7]

The rodent AFP system can be overridden with massive injections of estrogen, which overwhelm the AFP system and will masculinize the fetus. The masculinizing effect of estrogens may seem counter-intuitive since estrogens are critical for the proper development of female secondary characteristics during puberty. However, this is not the case prenatally. Gonadal hormones from the testes, such as testosterone and antimullerian hormone are required to cause development of a phenotypic male. Without these hormones the fetus will develop into a phenotypic female even if genetically XY. The conversion of testosterone into estradiol by aromatase in many tissues may be an important step in masculinization of that tissue.[8][9] Masculinization of the brain is thought to occur both by conversion of testosterone into estradiol by aromatase, but also by de novo synthesis of estrogens within the brain.[10][11] Thus, AFP may protect the fetus from maternal estradiol that would otherwise have a masculinizing effect on the fetus, but its exact role is still controversial.

Serum levels

Main article: Elevated alpha-fetoprotein

Maternal

In pregnant women, fetal AFP levels can be monitored in urine. Since AFP is quickly cleared from the mother's serum via her kidneys, maternal urine AFP correlates with fetal serum levels, although the maternal urine level is much lower than the fetal serum level. AFP levels rise until about week 32.

Infants

The normal range of AFP for adults and children is variously reported as under 50, under 10, and under 5 ng/mL.[12][13] 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.[14][15][16][17][18][19]

During this time, the normal range of AFP levels spans approximately 2 orders of magnitude.[16] Correct evaluation of abnormal AFP levels in infants must take into account these normal patterns.[16]

Very high AFP levels may be subject to hooking (see Tumor marker), which results in the level being reported significantly lower than the actual concentration.[20] 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.

Clinical significance

Main article: Elevated alpha-fetoprotein

Measurement of AFP is generally used in two clinical contexts. First, it is measured in pregnant women through the analysis of maternal blood or amniotic fluid as a screening test for certain developmental abnormalities such as aneuploidy. Second, serum AFP level is elevated in people with certain tumors, and so it is used as a biomarker to follow these diseases. Some of these diseases are listed below:

A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer properties.[27]

See also

References

  1. ↑ Tomasi TB (1977). "Structure and function of alpha-fetoprotein". Annual Review of Medicine. 28: 453–65. 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. 226 (5): 377–408. doi:10.1177/153537020122600503. PMID 11393167.
  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): 565–72. PMC 1685723. PMID 6192711.
  4. ↑ 4.0 4.1 "Entrez Gene: Alpha-fetoprotein".
  5. ↑ Pucci P, Siciliano R, Malorni A, Marino G, Tecce MF, Ceccarini C, Terrana B (May 1991). "Human alpha-fetoprotein primary structure: a mass spectrometric study". Biochemistry. 30 (20): 5061–6. doi:10.1021/bi00234a032. PMID 1709810.
  6. ↑ Seregni E, Botti C, Bombardieri E (1995). "Biochemical characteristics and clinical applications of alpha-fetoprotein isoforms". Anticancer Res. 15 (4): 1491–9. PMID 7544570.
  7. ↑ Carter CS (2002). "Neuroendocrinology of sexual behavior in the female". In Becker JB. Behavioral Endocrinology. Cambridge, Massachusetts: MIT Press. pp. 88–89. ISBN 0-262-52321-3.
  8. ↑ Nef S, Parada LF (December 2000). "Hormones in male sexual development". Genes Dev. 14 (24): 3075–86. doi:10.1101/gad.843800. PMID 11124800.
  9. ↑ Elbrecht A, Smith RG (1992). "Aromatase enzyme activity and sex determination in chickens". Science. 255 (5043): 467–70. doi:10.1126/science.1734525. PMID 1734525.
  10. ↑ Bakker J, Baum MJ (2008). "Role for estradiol in female-typical brain and behavioral sexual differentiation". Front Neuroendocrinol. 29 (1): 1–16. doi:10.1016/j.yfrne.2007.06.001. PMC 2373265. PMID 17720235.
  11. ↑ Harding CF (2004). "Hormonal modulation of singing: hormonal modulation of the songbird brain and singing behavior". Annals of the New York Academy of Sciences. 1016: 524–39. doi:10.1196/annals.1298.030. PMID 15313793.
  12. ↑ Ball D, Rose E, Alpert E (March 1992). "Alpha-fetoprotein levels in normal adults". Am. J. Med. Sci. 303 (3): 157–9. doi:10.1097/00000441-199203000-00004. PMID 1375809.
  13. ↑ Sizaret P, Martel N, Tuyns A, Reynaud S (February 1977). "Mean alpha-fetoprotein values of 1,333 males over 15 years by age groups". Digestion. 15 (2): 97–103. doi:10.1159/000197990. PMID 65304.
  14. ↑ Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U (1998). "Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age". Pediatr Hematol Oncol. 15 (2): 135–42. doi:10.3109/08880019809167228. PMID 9592840.
  15. ↑ Ohama K, Nagase H, Ogino K, Tsuchida K, Tanaka M, Kubo M, Horita S, Kawakami K, Ohmori M (October 1997). "Alpha-fetoprotein (AFP) levels in normal children". Eur J Pediatr Surg. 7 (5): 267–9. doi:10.1055/s-2008-1071168. PMID 9402482.
  16. ↑ 16.0 16.1 16.2 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): 19–25. doi:10.1097/00005176-198901000-00005. PMID 2471821.
  17. ↑ Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R (April 1987). "Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity". Arch. Dis. Child. 62 (4): 362–9. doi:10.1136/adc.62.4.362. PMC 1778344. PMID 2439023.
  18. ↑ Bader D, Riskin A, Vafsi O, Tamir A, Peskin B, Israel N, Merksamer R, Dar H, David M (November 2004). "Alpha-fetoprotein in the early neonatal period--a large study and review of the literature". Clin. Chim. Acta. 349 (1–2): 15–23. doi:10.1016/j.cccn.2004.06.020. PMID 15469851.
  19. ↑ 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. New York: Academic Press. pp. 111–122.
  20. ↑ Jassam N, Jones CM, Briscoe T, Horner JH (July 2006). "The hook effect: a need for constant vigilance". Ann. Clin. Biochem. 43 (Pt 4): 314–7. doi:10.1258/000456306777695726. PMID 16824284.
  21. ↑ Szabó M, Veress L, Münnich A, Papp Z (September 1990). "[Alpha fetoprotein concentration in the amniotic fluid in normal pregnancy and in pregnancy complicated by fetal anomaly]". Orv Hetil (in Hungarian). 131 (39): 2139–42. PMID 1699194.
  22. ↑ Rosen T, D'Alton ME (December 2005). "Down syndrome screening in the first and second trimesters: what do the data show?". Semin. Perinatol. 29 (6): 367–75. doi:10.1053/j.semperi.2006.01.001. PMID 16533649.
  23. ↑ 23.0 23.1 23.2 Le, Tao. First Aid for the USMLE Step 1 2013. New York: McGraw-Hill Medical, 2013. Print.
  24. ↑ Bredaki FE, Poon LC, Birdir C, Escalante D, Nicolaides KH (2012). "First-trimester screening for neural tube defects using alpha-fetoprotein". Fetal Diagn. Ther. 31 (2): 109–14. doi:10.1159/000335677. PMID 22377693.
  25. ↑ Ertle, JM; Heider, D; Wichert, M; Keller, B; Kueper, R; Hilgard, P; Gerken, G; Schlaak, JF (2013). "A combination of α-fetoprotein and des-γ-carboxy prothrombin is superior in detection of hepatocellular carcinoma". Digestion. 87 (2): 121–31. doi:10.1159/000346080. PMID 23406785.
  26. ↑ Taylor AM, Byrd PJ (October 2005). "Molecular pathology of ataxia telangiectasia". J. Clin. Pathol. 58 (10): 1009–15. doi:10.1136/jcp.2005.026062. PMC 1770730. PMID 16189143.
  27. ↑ Mesfin FB, Bennett JA, Jacobson HI, Zhu S, Andersen TT (April 2000). "Alpha-fetoprotein-derived antiestrotrophic octapeptide". Biochimica et Biophysica Acta. 1501 (1): 33–43. doi:10.1016/S0925-4439(00)00008-9. PMID 10727847.

Further reading

  • Nahon JL (1987). "The regulation of albumin and alpha-fetoprotein gene expression in mammals". Biochimie. 69 (5): 445–59. doi:10.1016/0300-9084(87)90082-4. PMID 2445387.
  • Tilghman SM (1989). "The structure and regulation of the alpha-fetoprotein and albumin genes". Oxf. Surv. Eukaryot. Genes. 2: 160–206. PMID 2474300.
  • Mizejewski GJ (2003). "Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy". Expert Rev Anticancer Ther. 2 (6): 709–35. doi:10.1586/14737140.2.6.709. PMID 12503217.
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