Tumor markers Tumor markers

Present; Present; by by

Dr. AndalibDr. AndalibIsfahan Medical SchoolIsfahan Medical School

•cancer is a broad term cancer is a broad term used to describe > 200 used to describe > 200 different diseases that different diseases that affect 50 tissuesaffect 50 tissues..

OverviewOverview

•Biological substances Biological substances synthesized and released by synthesized and released by cancer cells themselves or cancer cells themselves or produced by normal cells in produced by normal cells in response to tumor.response to tumor.

•Most tumor markers are Most tumor markers are proteinsproteins

•Tumor Specific Tumor Specific Transplantation Antigen Transplantation Antigen (TSTA)(TSTA)

•Tumor Specific Antigen Tumor Specific Antigen (TSA)(TSA)

Viral antigensViral antigens

proto oncogenesproto oncogenes

Tumor antigensTumor antigens

•Tumor Associated Antigens Tumor Associated Antigens (TAA) (TAA) of certain cancerous of certain cancerous tissue BUT large overlaptissue BUT large overlap

tissue differentiation antigenstissue differentiation antigens

gene products with increased expressiongene products with increased expression

altered glycoproteins and glycolipidsaltered glycoproteins and glycolipids

Altered expression of gene productsAltered expression of gene products

Oncofetal antigensOncofetal antigens

Tumor antigensTumor antigens

p. 526

• Screening of disease.Screening of disease.

• Diagnosis of symptomatic patients.Diagnosis of symptomatic patients.

• Staging of cancers.Staging of cancers.

• Prognostic indicators.Prognostic indicators.

• Detect recurrence in Follow-Up of Detect recurrence in Follow-Up of disease.disease.

• Monitoring response to therapy.Monitoring response to therapy.

Tumor antigens could be Tumor antigens could be used forused for

Tumor markerTumor marker

• First tumour markerFirst tumour marker

• 19381938

• Acid phosphatase for metastatic Acid phosphatase for metastatic prostateprostate

Tumor markersTumor markers• Are biochemical substances which, as the name Are biochemical substances which, as the name

suggest, are closely associated with suggest, are closely associated with carcinogenesiscarcinogenesis

• Are substances, such as proteins, biochemical, or Are substances, such as proteins, biochemical, or enzymes, produced by tumor cells or by the body enzymes, produced by tumor cells or by the body cells in response to tumor cellscells in response to tumor cells

• Are substances that can often be detected in Are substances that can often be detected in higher than normal in the blood, urine, or body higher than normal in the blood, urine, or body tissues of some patients with certain types of tissues of some patients with certain types of cancercancer

• Substances present in or produced by a tumor Substances present in or produced by a tumor itself or produced by the host in response to a itself or produced by the host in response to a tumortumor

Tumor markersTumor markers

• Measurement of tumor markers: Measurement of tumor markers: helpfulhelpful

• Tumor marker levels could elevated in Tumor marker levels could elevated in benign conditionsbenign conditions

• Many tumor markers are not specific Many tumor markers are not specific to a particular type of cancerto a particular type of cancer– In addition diagnosis :help In addition diagnosis :help

physicians make a plan for physicians make a plan for appropriate therapyappropriate therapy

Tumor markersTumor markers

• Used to differentiate tumor from normal Used to differentiate tumor from normal tissuetissue

• Determine presence of tumor based on Determine presence of tumor based on quantity in blood or secretionsquantity in blood or secretions

• Higher quantity in cancer tissue, or in Higher quantity in cancer tissue, or in blood from cancer patient, then in benign blood from cancer patient, then in benign tumors or normal individualstumors or normal individuals

• Few tumor markers are specific for a Few tumor markers are specific for a single type of tumorsingle type of tumor

Tumor markersTumor markers

• Most markers are found in many Most markers are found in many different types of tumordifferent types of tumor

• Monitor a patient response to Monitor a patient response to treatmenttreatment

• After treatment :as a part of follow up After treatment :as a part of follow up care to check for recurrencecare to check for recurrence

• Decrease or return to normal: Decrease or return to normal: favorable response to therapyfavorable response to therapy

Tumor marker classificationTumor marker classification

• Tumor antigensTumor antigens

• EnzymesEnzymes

• HormonesHormones

• Oncogene Oncogene productsproducts

OncofetalOncofetalReceptorsReceptorsGenetic markersGenetic markers

Tumor antigens-OncofetalTumor antigens-Oncofetal

• Oncofetal:produced during normal Oncofetal:produced during normal emberyogical development and by emberyogical development and by neoplastic cellsneoplastic cells

• Defined by polyclonal or monoclonal Defined by polyclonal or monoclonal antibodiesantibodies

• CEA, AFP, HCGCEA, AFP, HCG

Tumor associated antigensTumor associated antigens(Cancer antigen)(Cancer antigen)

• CA 125CA 125

• Ca 19-9Ca 19-9

• CA 15-3CA 15-3

• CA 27-29CA 27-29

• CA 50CA 50

• CA 242CA 242

ENZYMESENZYMES

• Neuron specific enolase(NSE)Neuron specific enolase(NSE)

• Acid phosphataseAcid phosphatase

• Lactic dehydrogenaseLactic dehydrogenase

Dunn et al. Nature Reviews Immunology 6, 836–848 (November 2006) | doi:10.1038/nri1961

HormonesHormones

* Human Chorionic Gonadotrophins * Human Chorionic Gonadotrophins

(HCG)(HCG)

are secreted in are secreted in

Choriocarcinoma, Ovarian CancerChoriocarcinoma, Ovarian Cancer

* Thyroxin is secreted in thyroid * Thyroxin is secreted in thyroid

cancer cancer

Ideal markersIdeal markers

• Present in early in diseasePresent in early in disease

• Before clinical evidence of diseaseBefore clinical evidence of disease

• Increase with advancing tumorIncrease with advancing tumor

• Decrease with effective therapyDecrease with effective therapy

• Test reproducibleTest reproducible

• Available and cost effectiveAvailable and cost effective

Ideal marker Ideal marker

• Specific: produced only by cells of a Specific: produced only by cells of a particular malignancy and not by particular malignancy and not by other cancers, or benign conditionsother cancers, or benign conditions

• Sensitive: produced in all patient Sensitive: produced in all patient with similar malignancywith similar malignancy

Specific organ tumor Specific organ tumor systemssystems

• Gastrointestinal tumorsGastrointestinal tumors

• CEACEA

• AFPAFP

• CA19-9CA19-9

PSAPSA

Prostate specificProstate specific antigenantigen

PSAPSA

• In low concentration in the blood of all In low concentration in the blood of all adult malesadult males

• Is produced both normal and abnormal Is produced both normal and abnormal prostate cellsprostate cells

• Elevated PSA levels: in blood of men Elevated PSA levels: in blood of men with benign prostate condition with benign prostate condition

• Prostatitis/benign hyperplasia/malignantProstatitis/benign hyperplasia/malignant

PSAPSA

• PSA level:monitoring the PSA level:monitoring the effectiveness of prostate cancer effectiveness of prostate cancer treatment treatment

• Checking recurrence after treatmentChecking recurrence after treatment

PSA PSA As a screen for prostate As a screen for prostate cancer or in the elevation cancer or in the elevation of or to follow up a person of or to follow up a person with prostate diseasewith prostate disease

CA 27-29CA 27-29

Cancer antigen 27-29Cancer antigen 27-29

For Breast cancerFor Breast cancer

CA 27-29CA 27-29

• Breast cancerBreast cancer

• Check for recurrence in woman previously Check for recurrence in woman previously treated for stage 2 and stage 3 breast cancertreated for stage 2 and stage 3 breast cancer

• Colon/stomach/kidney/lung/ovary/Colon/stomach/kidney/lung/ovary/

• pancreas/uterus/liverpancreas/uterus/liver

• Nan-cancerous: first trimester Nan-cancerous: first trimester pregnancy/endometritis/ovarian cysts/benign pregnancy/endometritis/ovarian cysts/benign breast disease/kidney disease/liver disease breast disease/kidney disease/liver disease

TitleTitle

NSENSE

Neuron-specificNeuron-specific enolaseenolase

NeuroblastomaNeuroblastoma

NSENSE

• Neuroblastoma/small cell lung Neuroblastoma/small cell lung cancer/wilms cancer/wilms tumor/melanoma/cancers of tumor/melanoma/cancers of thyroid/kidney/testicule/pancreasthyroid/kidney/testicule/pancreas

• Patient prognosisPatient prognosis

• Patient response to treatmentPatient response to treatment

CEACEA

Carcino-Emberyonic Carcino-Emberyonic AntigenAntigen

CEACEA

• Oncofetal proteinOncofetal protein• Normal during fetal life(low concentration Normal during fetal life(low concentration

in healthy adults)in healthy adults)• Higher concentration in some epithelial Higher concentration in some epithelial

malignanciesmalignancies• Glycoprotein(molecular weight Glycoprotein(molecular weight

200,000KD)200,000KD)

CEACEA

•Found on cell membraneFound on cell membrane•Easily released into fluidsEasily released into fluids•Related to immunoglobolin Related to immunoglobolin

super-family genessuper-family genes•Normally found in mucus Normally found in mucus

secretions of the stomach, small secretions of the stomach, small intestine intestine

CEACEA

• Small amount in the blood of healthy peopleSmall amount in the blood of healthy people

• Primary use of CEA: in monitoring colorectal Primary use of CEA: in monitoring colorectal cancercancer

• Melanoma/lymphoma/breast/lung/Melanoma/lymphoma/breast/lung/pancreas/stomach/cervix/bladder/kidney/pancreas/stomach/cervix/bladder/kidney/thyroid/liver/ovarythyroid/liver/ovary

• Nan-cancerous condition: inflammatory Nan-cancerous condition: inflammatory bowel disease/pancreatitis/liver diseasebowel disease/pancreatitis/liver disease

• Tobacco usersTobacco users

CEACEA

• lOW SPECIFICITY and lOW lOW SPECIFICITY and lOW SENSITIVITYSENSITIVITY

AFPAFP

• Alpha-fetoproteinAlpha-fetoprotein

AFPAFP

• First described oncofetal antigenFirst described oncofetal antigen• Normally: by a developing fetusNormally: by a developing fetus• AFP level :elevated :liver AFP level :elevated :liver

cancer/germ cell cancer/germ cell cancer/ovary/testiculecancer/ovary/testicule

• Non-cancerous condition: benign Non-cancerous condition: benign liver condition /cirrohosis or liver condition /cirrohosis or hepatitis/pregnancyhepatitis/pregnancy

CA 19-9CA 19-9

CancerCancer antigen 19-9 antigen 19-9

CA 19-9CA 19-9

• A carbohydrated antigen detected by A carbohydrated antigen detected by monoclonal antibodiesmonoclonal antibodies

• Pancreatic cancerPancreatic cancer

• Biliary tract cancerBiliary tract cancer

• Billary tract diseaseBillary tract disease

• pancreatitispancreatitis

TUMOR MARKERTUMOR MARKER

• Screening Screening

• DiagnosisDiagnosis

• PrognosisPrognosis

• monitoringmonitoring

CA 125CA 125

CancerCancer antigenantigen 125 125

ovarian cancerovarian cancer

CA 125CA 125

• Is produced by a variety of Is produced by a variety of cells(ovarian cancer)cells(ovarian cancer)

• Is used primarily in the management Is used primarily in the management and treatment of ovarian cancerand treatment of ovarian cancer

• In woman with ovarian cancer: In woman with ovarian cancer: chemotherapychemotherapy

CA125CA125

• Falling CA125 levels generally Falling CA125 levels generally indicates that cancer is responding to indicates that cancer is responding to treatmenttreatment

• Increasing CA125 levels during or Increasing CA125 levels during or after treatment: is not responding to after treatment: is not responding to therapytherapy

CA 125CA 125

• To monitor for recurrence of ovarian To monitor for recurrence of ovarian cancercancer

• Uterus/cervix/pancease/liver/colon/Uterus/cervix/pancease/liver/colon/breast/lung/digestive tractbreast/lung/digestive tract

• Non-cancerous condition: elevated Non-cancerous condition: elevated CA125(endometriosis/pelvic inflammatory CA125(endometriosis/pelvic inflammatory disease/peritonitis/liver diseasedisease/peritonitis/liver disease

• Menstruation and pregnancy Menstruation and pregnancy

HCGHCG

Human chorionic Human chorionic gonadotropinegonadotropine

HCGHCG

• Is produced by placenta during Is produced by placenta during pregnancypregnancy

• For screen choriocarcinomaFor screen choriocarcinoma

• Monitoring the treatment of trophoblastic Monitoring the treatment of trophoblastic diseasedisease

• Elevated HCG Elevated HCG level:testis/ovary/liver/stomach/pancreas/level:testis/ovary/liver/stomach/pancreas/

• lung/pregnancy/marijuanalung/pregnancy/marijuana

CA 15-3CA 15-3

Cancer antigen 15-3Cancer antigen 15-3

breast cancerbreast cancer

CA 15-3CA 15-3

• In following the course of treatment in women In following the course of treatment in women diagnosis with breast cancer(advance)diagnosis with breast cancer(advance)

• Early stage breast cancerEarly stage breast cancer

• Ovary/lung/prostateOvary/lung/prostate

• Non-cancerous condition: benign Non-cancerous condition: benign breast/ovarian disease /endometrisis/pelvic breast/ovarian disease /endometrisis/pelvic inflammatory disease/hepatitisinflammatory disease/hepatitis

• PregnancyPregnancy

Tumor markerTumor marker

• Screen and diagnose cancerScreen and diagnose cancer

• Predicting prognosisPredicting prognosis

• Monitor treatmentMonitor treatment

• observation for cancer recurrenceobservation for cancer recurrence

RealtyRealty

• No marker to date satisfy these No marker to date satisfy these criteriacriteria

Thank youThank you