relevance of serum tumor markers

8/8/2019 Relevance of Serum Tumor Markers

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RELEVANCE OF SERUMTUMOR MARKERS


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1846 Bence-Jones protein

19401940 Acid phosphataseAcid phosphatase

1960 Immunoassay

19631963 AlphaAlpha--fetoproteinfetoprotein1965 Carcinoembryonic antigen

19751975 Monoclonal antibodiesMonoclonal antibodies

1980 CA 125, PSA, Carbohydrate antigens

19701970 OncogenesOncogenes1980 Tumor Suppressor Genes

20012001Microarrays, Mass Spectrometry, NeuralMicroarrays, Mass Spectrometry, Neural

Networks, Networks, MultiparametricMultiparametric AnalysisAnalysis


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Are substances usually proteins, that areproduced by the body in response to cancergrowth or by the cancer tissue itself and certain

benign (noncancerous) conditionsDetected in higher than normal amounts in theblood, urine, or body tissuesSome tumor markers are specific for one type of

cancer, while others are seen in several cancertypesMeasurements can be useful when used alongwith x-rays, or other tests in the detection and

diagnosis of some types of cancer


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H ighly specific : detectable in only one tumor typeH ighly sensitive : non-detectable in physiological orbenign disease statesLong lead-time : sufficient time for alteration ofnatural course of diseaseLevels correlate with tumor burden : prognostic &predictive utility of tumor markerShort half-life : frequent serial monitoring of markerlevels after 5-6 half-livesSimple and cheap test : applicability as screening testEasily obtainable specimens : acceptability by targetpopulation

I N REAL I TY AN ID EAL TUMOR MARKER D OES NOT EX I ST


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Serology Enzyme assaysImmunological Immunohistochemistry

Radioimmunoassay

Enzyme-linked immunosorbent assay

Flow cytometry

Cytogenetic analysis Flourescent in-situ hybridization

Spectral karyotyping

Comparative genomic hybridization

Genetic analysis Sequencing (automated)

Reverse transcriptionGel electrophoresis

DNA micro-array analysis

Proteomics Surface-enhanced laserdesorption/ionization


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CATEGORY SUBCATEGORY EXAMPLESO ncofetal antigens AFP, CEAH ormones Catecholamines, calcitonin,,

B-H CG

Glycoproteins CA125, CA15-3, CA19-9, CA72-4,PSA

Metabolites VMA, H IAA

Tumor-associated antigens Viral antigens Polyoma, SV 40

MH C-related antigens H -2k antigen

Enzymes NSE, PLAPO ncogene products C-myc, c-erbB2

Cytogenetic products Philadelphia chromosome

Tumor-associated markers Proteins Immunoglobulins, B-2M`

Enzymes Lactate dehydrogenase, alkaline

phosphatase, pteridines, pterinesAcute-phase proteins C-reactive protein, ferritin

Inflammatory markers ESR, viscosity

Ultrastructural components Intermediate filamentcomponents

Desmin, vimentin


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SCREEN I NG

DI AGNOS I S

PROGNOS I S: RECURRENCE,METASTAS I S AN D SURV I VAL

MON I TOR I NG TREATMENTRESPONSE


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Never rely on the result of a single test When ordering serial testing, be certain to order every test fromthe same laboratory using the same assay kit Be certain that the tumor marker selected for monitoring

recurrence was elevated in the patient prior to surgery Consider the half-life of the tumor marker when interpreting thetest result Consider how the tumor marker is removed from ormetabolized in the blood circulationConsider ordering multiple markers to improve both thesensitivity and the specificity for diagnosisBe aware of the presence of ectopic tumor markersHeterophile antibody


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A complex glycoprotein with a MW of approximately 180,000 daltons

First discovered in patients with adenocarcinoma of the colon in 1965

Metabolized primarily by the liver with a circulating half-life rangingfrom 1 to 8 days

H epatic diseases, including extrahepatic biliary obstruction,intrahepatic cholestasis and hepatocellular disease, may impedeclearance rate

Normally, it is present in the fetal intestine, pancreas and liverduring the first 2 trimesters of gestation

Normal colonic mucosa and pleural and lactating mammary tissuebind to anti-CEA antiserum; however, the quantity of CEA or CEA-like molecules expressed in these tissues is much less than thatobserved in malignant tumors

Normal range is from 0 to 2.5 to 3.0 ng/ml as determined byradioimmunoassays and increase serum concentrations


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Benign conditions that cause elevated CEA

Cigarette smoking BronchitisEmphysema GastritisGastric ulcer H epatic diseasePancreatitis Polyps of colon& rectumDiverticulitis Crohns diseaseBPH Renal disease


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An oncofetal protein that was first discovered in1963 in the serum of mice with hepatomaNormal fetal protein synthesized by the liver, yolksac, and GIT that shares sequence homology with

albuminA major component of fetal plasma, reaching apeak concentration of 3mg/ml at 12 weeks ofgestation -- following birth, it clears rapidly fromthe circulation, having a half-life of 3.5 daysConcentration in adult serum


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Malignant conditions causingelevation of AFP aside from hepatoma

Teratocarcinoma of the testis andembryonal Ca (70%)Carcinoma of the pancreas (23%)Carcinoma of the stomach (18%)Carcinoma of the lung (7%)Carcinoma of the colon (5%)

*** In patients with hepatoma, theincidence of elevation of levels of AFPcorrelates with tumor burden


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A glycoprotein hormone with a MW of 45,000 daltonsComposed of 2 polypeptide chain alpha and betaCirculating half-life is 12 to 20 hoursNormally secreted by placental tissue with highestcirculating levels occurring at 60 days of gestationSignificant elevation occurs during pregnancy and inpatients with trophoblastic neoplasms ornonseminomatous germ cell tumorsIt maybe secreted in small amounts by the testis, pituitarygland and GITMaybe elevated in some benign conditions peptic ulcerdisease, inflammatory intestinal disease and cirrhosisIn patients with trophoblastic disease, levels of H CGcorrelate with tumor burden, prognosis of patient andresponse to therapy


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An antigen present on 80% of non-mucinous ovarian carcinomasDefined by a monoclonal antibody ( O C125)

that was generated by immunizinglaboratory mice with a cell line establishedfrom human ovarian carcinomaElevated in other cancers endometrial,

pancreatic, lung, breast, and colonElevated in benign conditions menstruation, pregnancy, endometriosis


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A monoclonal antibody generatedagainst a colon carcinoma cell line

to detect a monosialogangliosidefound in patients withgastrointestinal adenocarcinoma

Elevated in gastric cancer (21-42%), colon cancer (20-40%),pancreatic cancer (71-93%)


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Found in normal prostatic epithelium and secretions butnot in other tissuesIt is a glycoprotein whose function may be to lyse theseminal clotH ighly sensitive for the presence of prostatic cancerElevation correlated with stage and tumor volumePredictive of recurrence and response to treatmentH as prognostic value in patients with very high valuesprior to surgery are likely to relapsePresent in low concentrations in the blood of adult malesIt is produced by both normal and abnormal prostatecellsBenign elevations prostatitis and BP H


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TumorTumorMarkersMarkers

CancersCancers What else? What else? SampleSample

B2M (BetaB2M (Beta--22microglobulinmicroglobulin

MultipleMultiplemyeloma,myeloma,lymphomaslymphomas

CrohnsCrohnsdisease,disease,hepatitishepatitis

BloodBlood

BTA (BladderBTA (Bladdertumor antigentumor antigen

BladderBladder GainingGainingacceptanceacceptance

UrineUrine

CA 72CA 72--44(Cancer(Cancerantigen 72antigen 72--44

O varianO varian No evidenceNo evidencethat is betterthat is betterthan CA 125than CA 125

BloodBlood


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TumorTumorMarkersMarkers

CancersCancers What else?What else? SampleSample

CalcitoninCalcitonin ThyroidThyroidMedullaryMedullarycarcinomacarcinoma

Also elevated in Also elevated inperniciousperniciousanemia andanemia andthyroiditsthyroidits

BloodBlood

NSE (NeuronNSE (Neuron--specificspecific enolaseenolase

Neuroblastoma,Neuroblastoma,small lungsmall lungcancercancer

May be betterMay be betterthan CEA for ff.than CEA for ff.this kind of lungthis kind of lungcancercancer

BloodBlood

NMP22NMP22 BladderBladder Not widely usedNot widely used UrineUrine

ProstateProstate- -specificspecificmembranemembraneantigen (PSMA)antigen (PSMA)

ProstateProstate Not widely used,Not widely used,levels increaselevels increasenormally withnormally withageage

BloodBlood


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Ectopic tumor marker Primary tumor siteAFP Gastrointestinal, renal, breast, bladder &

ovary carcinoma

Calcitonin Carcinoma of lung, islet cell, carcinoid,breast and ovary, medullary carcinoma,phaeochromocytoma

Chromogranin A For endocrine tumors (medullary thyroidcarcinoma, anterior pituitary adenoma,pancreatic islet-cell carcinoma)

Beta-H CG Gastric & pancreatic carcinomas,hepatoma, ovarian adenocarcinoma,germinal-cell tumors of testis

hyroglobulin hyroid carcinoma


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relevance of serum tumor markers

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