Carcinoembryonicantigen(serum)

1.1

1.2

1.3

1.4

1.5

2.1

2.2

3.1

Nameanddescriptionofanalyte
Nameofanalyte
Carcinoembryonicantigen(CEA)
Alternativenames
None
NMLCcode
Descriptionofanalyte

CEAisaglycoproteinofMWapprox.180kDfoundinnormalfetal
gastrointestinaltissue;itisnormallypresentatonlyverylow
concentrationsinadultplasmabutitsconcentrationisincreasedinthe
presenceofmanytumours,particularlycolorectalcancers(70%).
Increasedconcentrationshavealsobeendescribedingastric,bronchial,
uterineandovariancancers,andinlymphomas.
Functionofanalyte.
ThenormalfunctionofCEAisunknown.
Samplerequirementsandprecautions
Mediuminwhichmeasured
CEAismeasuredinserum.
Precautionsresampling,handlingetc.
Generalprecautionsonly.
Summaryofclinicalusesandlimitationsofmeasurements

Use
CEAisrecommendedforuseonlytomonitorpossiblerecurrenceinsome
patientsfollowingresectionofcolorectalcancer.Itisnotrecommendedas
adiagnostictest.

3.2 Limitations
1.CEAisinsufficientlysensitiveorspecifictobeofvalueinscreeningfor
ordiagnosingcolorectalcancer.
2.CEAhasbeenusedextensivelyformonitoringtumoursotherthan
colorectalbutisnotrecommendedforthispurposeandinmanyinstances
superiormarkersarenowavailable.

4 Analyticalconsiderations

4.1 Analyticalmethod

CEAismeasuredbyimmunoassay.

4.2 Referencemethod

Nonereported.
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4.3

4.4

Referencematerials:TheWHOExpertCommitteeonBiological
Standardisationhasestablishedthepreparationcoded73/601(National
InstituteforBiologicalStandardsandControl,USA)asthe1st
InternationalReferencePreparationofCEA.

Interference
Aswithallimmunometricassays,thereisapotentialforinterferenceby
invivoheterophilicantibodies.Resultsmustalwaysbeconsideredin
relationtotheclinicalsituationandtopreviousassayresults,ifavailable.
Thelatterisparticularlyimportantwhenserialresultsarebeingusedfor
monitoringtheresponsetotreatment.

4.5 Sourcesoferror
Atveryhighconcentrations,thereisariskofassaysgeneratingfalsely
lowvaluesasaresultofthehighdosehookeffect.

5
Referenceintervalsandvariance

5.1.1 Referenceinterval:theupperreferencelimitis~2.5g/L
5.1.2 Referenceintervals(others):theupperreferencelimitinsmokersis~5.0
g/L
5.1.3 Extentofvariation
5.1.3.1 InterindividualCV:thisisnotausefulconceptwithtumourmarkers
5.1.3.2 IntraindividualCV:13%
5.1.3.3 CVofmethod:5%
5.1.3.4 Criticaldifference:~36%
5.1.4 Sourcesofvariation
[CEA]isincreasedinsmokersandinsomepatientswithinflammatory
boweldiseaseandchronicliverdisease.

6
Clinicalusesofmeasurementandinterpretationofresults

6.1 Usesandinterpretation

CEAisonlyrecommendedformonitoringcertainpatientsfollowing
resectionofcolorectalcancer.Itshouldnotbeusedforscreeningor
diagnosis.Aconcentration>50g/Liseffectivelydiagnosticofmetastases
beingpresent.

Thehalflifeinplasmaisapproximately4.5days.Alongerapparenthalf

lifefollowingsurgerysuggestsincompleteresection.

6.2 Confoundingfactors
1.ThespecificityofCEA(3080%)forcolorectalcanceriscompromised
byitsplasmaconcentrationnotbeingconsistentlyelevatedincolorectal
cancer:itmaybeundetectableorpresentatonlylowconcentrationswith
poorlydifferentiatedtumours.
2.ThesensitivityofCEA(~40%)forcolorectalcanceriscompromisedby
itsbeingdetectableinsomebenign,conditions(particularly
gastrointestinal)andinsomenoncolorectaltumours,e.g.gastric,cervical
andnonsmallcellbronchialcarcinomas.
3.SmokersfrequentlyhavehigherplasmaconcentrationsofCEAthan
nonsmokers(typicallyuptotwicethevalue).

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7 Causesofabnormalresults

7.1 Highvalues
7.1.1Causes
Highvaluesarefoundinmany,butnotall,patientswithcolorectal
carcinomaandlessfrequentlyinavarietyofothertumoursaswellas
occasionallyinbenignconditions.SincemmeasurementofCEAshould
notbeusedasascreeningtest(i.e.intheabsenceofclinicalevidence
ofcancer)theactiontobetakenifanunexpectedlyhigh[CEA]isfound
willnotbeconsideredhere.
Afailureofanelevated[CEA]tofallfollowingsurgicalresectionofa
tumoursuggestseitherincompleteresection,localrecurrenceorthe
presenceofhepaticmetastases.[CEA]increaseslessfrequentlywith
metastasestothelungs.
Ariseinconcentrationof1g/Lfollowinganinitialfallafterresection
(evenifthesecondresultisbelowtheupperreferencelimit)suggests
recurrenceormetastasis(sensitivity80%,specificity86%).

7.1.2 Investigation
IfCEAismisusedasascreeningtestforcancerandahighvalueisfound,
theappropriatefurtherinvestigationwilldependonanyclinicalfindings.
Inanasymptomaticnonsmoker,withonlyaslightlyelevatedvalue,a
pragmaticapproachwouldbetorepeatthetestafteronemonth:arising
valuewouldbemorelikelytorepresentmalignancythanastableone.

7.2 Lowvalues
7.2.1 Causes
CEAshouldbeundetectableorpresentinonlyverylowconcentrationsin
healthyindividuals;theconceptofalowvalueisnotapplicable.

7.3
Note
Aswithalltumourmarkers,afallinconcentrationorthedisappearance
ofCEAfromtheplasmamaybeduetoachangeinthetumoursuchthat
CEAisnolongerexpressed.Thisappearstobeanunusualphenomenon
withcolorectalcancers.

8 Performance

8.1
Sensitivity,specificityetc:see6.2forcolorectalcancer;valuesarelower
forothertumours.

9 Systematicreviewsandguidelines

9.1Systematicreviews

Noneidentified.

9.2Guidelines
Publishedguidelinesandrecommendationsareinbroadagreementthat
CEAmeasurementsshouldonlybeusedaspartoffollowupfor
attemptedcurativesurgeryincolorectalcancer(e.g.SIGNGuidelineno
67:ManagementofColorectalCancer:March2003updatedSeptember
2011http://www.sign.ac.uk/guidelines/fulltext/67/index.html).The
evidencesuggeststhatusingCEAforthispurposeallowsdetectionof
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recurrenceormetastasissomesixmonthsearlierthanifitisnotused.
Thereis,however,inconsistentevidenceastowhethermeasuringCEAin
thiswayaffectsclinicaloutcome.

AtkinsCD.Guidelinesfortheuseofcarcinoembryonicantigenin

colorectalcancer.JournalofClinicalOncology1997,15:863864.
ScheerRA,AuerRA.Surveillanceaftercurativesurgeryofcolorectal
cancer.ClinicalColonicandRectalSurgery2009;22:242250(includes
summaryofcurrentpublishedguidelines).

9.3Recommendations
1.TheAmericanSocietyofClinicalOncologyrecommendsthatCEA
concentrationsaremeasuredatthreemonthlyintervalsforatleastthree
yearsinpatientswithDukesstageBorCdiseasewhowouldbe
candidatesforliverresection,andtomonitormetastaticdiseaseduring
systemictreatment.Itisnotrecommendedforscreeningorasaguideto
adjuvanttreatment.(http://www.guidelines.gov/context.aspx?id=20014)
accessed20.i.2010.

2.Theserecommendationsaresupportedinotherdocuments,e.g.
a.DuffyMJ.Carcinoembryonicantigenasamarkerforcolorectalcancer:
isitclinicallyuseful?ClinicalChemistry2001,47:624630.
b.VanCutsemE,DicatoMArberNetal.Molecularmarkersandbiological
targetedtherapiesinmetastaticcolorectalcancer:expertopinionand
recommendationsderivedfromthe11thESMO/WorldCongresson
GastrointestinalCancer,Barcelona,2009.AnnOncol2010Suppl6:vi1
vi10.

10
Links

10.1Relatedanalytes:numeroustumourmarkershavebeendescribedbut

CEAhasthebestperformanceforcolorectalcancer.Particularlyforthe

newermarkers,thereisconsiderableoverlapbetweenthetumourtypes

inwhichagivenmarkermaybedetectable,markersmaybeundetectable

eveninthepresenceofclinicaldisease(poorsensitivity)andtheir

concentrationsmaybeincreasedinbenignconditions(poorspecificity).

10.2Relatedtests:see6.3

10.3 Note
IntheUK,thereisanationalscreeningprogrammeforcolorectalcancer
basedonthedetectionofstooloccultbloodwithfollowupofpositive
resultsusingflexiblecolonoscopy.

Author:WilliamMarshall

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