Post on 26-Mar-2015
Dr. Amal S. AhmedAss Prof.Clinical Pathology
Suez Canal University
Historical background of tumor markersHistorical background of tumor markers
The first TM reported was Bence Jones protein. Since The first TM reported was Bence Jones protein. Since its discovery in 1847 by precipitation of a protein in its discovery in 1847 by precipitation of a protein in acidified boiled urine , the measurement of B.J.P has acidified boiled urine , the measurement of B.J.P has been a diagnostic test for Multiple myloma (plasma been a diagnostic test for Multiple myloma (plasma cell tumor).cell tumor).
The general application of TM for monitoring cancer The general application of TM for monitoring cancer patient start with the discovery of AFP in 1963 and patient start with the discovery of AFP in 1963 and CEA in 1965.CEA in 1965.
Definition of TMDefinition of TM
A substance produced or induced by tumor cells and A substance produced or induced by tumor cells and released into blood , body fluids or expressed on cell released into blood , body fluids or expressed on cell surface , that can be used to differentiate a tumor from surface , that can be used to differentiate a tumor from normal tissue or to determine the presence of a tumor.normal tissue or to determine the presence of a tumor.
Few markers are specific for a single individual tumorFew markers are specific for a single individual tumor
( ( tumor-specific markerstumor-specific markers) ) Most are found with different tumors of the same tissue Most are found with different tumors of the same tissue
typetype
( ( tumor-associated markerstumor-associated markers) )
Classification of TMClassification of TM
Enzymes & isoenzymes Hormones Oncofetal antigens Carbohydrates markers Proteins Receptors & other markers Genetic markers (Oncogenes & suppressor gene mutations )
Potential uses of TMPotential uses of TM
Screening in general population Clinical staging of cancer Prognostic indicator for disease progress Evaluation of treatment success Detection the recurrence of cancer Monitoring response to therapy Radioimmunolocalization of tumor
Recommended Cancer ScreeningRecommended Cancer ScreeningTestsTests
CancerTechnique
BreastMammography
CRCASigmoidoscopy
CervicalPAP
NeuroblastomaVMA
HCCAFP
ProstatePSA
OvarianCA 125
Predictive MarkersPredictive Markers
ER and PR: For predicting response toER and PR: For predicting response to
hormone therapy in breast cancerhormone therapy in breast cancer
HER-2: For predicting response toHER-2: For predicting response to
trastuzumab (Herceptin) in breast cancertrastuzumab (Herceptin) in breast cancer
Disease ManagementDisease Management
Most TM are usedMost TM are used to monitor treatment and to monitor treatment and progression of cancer .progression of cancer .
Single determination does not allow definite Single determination does not allow definite conclusion.conclusion.
Combining different markers can improve the Combining different markers can improve the diagnostic precision.diagnostic precision.
Normal level ( negative result ) does not exclude Normal level ( negative result ) does not exclude malignancy.malignancy.
Enzymes & Isoenzymes
TMTMcancercancer
AldolaseAldolaseLiverLiver
AmylaseAmylasePancreaticPancreatic
AlpAlpLiver, Bone, leukemia & lymphomaLiver, Bone, leukemia & lymphoma
CK-BBCK-BBProstate, lung , breast, colon, ovaryProstate, lung , breast, colon, ovary
LDHLDHLiver, leukemia & lymphomaLiver, leukemia & lymphoma
GGTGGTLiverLiver
PSA&PAPPSA&PAPProstateProstate
ElastaseElastasebreastbreast
HormonesTMTMcancercancer
ACTHACTHCushingCushing’’s & Lungs & Lung
ADHADHLung, adrenal cortex, pancreasLung, adrenal cortex, pancreas
PTHPTHLiver, renal, breast, lungLiver, renal, breast, lung
CalcitoninCalcitoninMedullary thyroidMedullary thyroid
GastrinGastrinGlucagonomaGlucagonoma
GHGHPituitary, renal , lungPituitary, renal , lung
hCGhCGchoriocarcinomachoriocarcinoma
ProlactinProlactinPituitary, renal , lungPituitary, renal , lung
Oncofetal Ags :Oncofetal Ags :Normally produced proteins during fetal life, decrease to low levels or disappear after birth and reappear in cancer patients
TMTMcancercancer
AFPAFPHCC, germ cell carcinomaHCC, germ cell carcinoma
CEACEAColorectal, GIT, pancreas, lung, breastColorectal, GIT, pancreas, lung, breast
Carcinofetal Carcinofetal ferritinferritin
LiverLiver
Squamous cell AgSquamous cell AgCervix, lung, skin, head & neckCervix, lung, skin, head & neck
Carbohydrate markers: Carbohydrate markers: Either are antigens on the tumor cell surface or are Either are antigens on the tumor cell surface or are secreted by the tumor cellssecreted by the tumor cellsThey are high molecular weight mucins or blood They are high molecular weight mucins or blood group antigensgroup antigens
TMTMcancercancer
CA 125CA 125Ovarian , endometrialOvarian , endometrial
CA 15-3CA 15-3Breast , ovarianBreast , ovarian
CA 19-9CA 19-9Pancreatic , gastrointestinal , hepaticPancreatic , gastrointestinal , hepatic
CA 19-5CA 19-5Gastrointestinal , Pancreatic , ovarianGastrointestinal , Pancreatic , ovarian
CA 50CA 50Pancreatic , gastrointestinal , colonPancreatic , gastrointestinal , colon
Proteins TMProteins TM
TMTMcancercancer
BB2-microglobulin2-microglobulinMM ,B-cell lymphoma ,CLLMM ,B-cell lymphoma ,CLL
C-peptideC-peptideInsulinomaInsulinoma
FerritinFerritinLiver, lung, breast, leukemiaLiver, lung, breast, leukemia
immunoglobulinimmunoglobulinMM , lymphomasMM , lymphomas
Other tumor markersOther tumor markers
TMTMNatureNatureCancerCancer
Estrogen & Estrogen & progesterone receptorsprogesterone receptors
TissueTissueBreastBreast
CatecholamineCatecholamine metabolitesmetabolites
Urine ( VMA , HVA )Urine ( VMA , HVA )Nuroblastoma , Nuroblastoma , phyochromocytomaphyochromocytoma
HydroxypolineHydroxypolineUrineUrineBone metastasis Bone metastasis (breast) , MM(breast) , MM
Genetic MarkersGenetic Markers
Two classes of genes are involved in the development of Two classes of genes are involved in the development of cancer :cancer :
1.1. Oncogens :Oncogens :
cell activation genes that code for products involved in cell activation genes that code for products involved in normal cellular processes such as growth factor signaling normal cellular processes such as growth factor signaling pathways.pathways.
over expression ( activation ) of oncogens will lead to over expression ( activation ) of oncogens will lead to abnormal cell growth , resulting in malignancy (mostly abnormal cell growth , resulting in malignancy (mostly hematological malignancy ).hematological malignancy ).
Some oncogens found in human tumorsSome oncogens found in human tumors
oncogenoncogenfunctionfunctioncancercancer
N-ras mutationN-ras mutationSignal transductionSignal transductionAML, nuroblastomaAML, nuroblastoma
K-ras mutationK-ras mutationSignal transductionSignal transductionLeukemia, Leukemia, lymphomalymphoma
bcl-2bcl-2Blocks apoptosisBlocks apoptosisLeukemia, Leukemia, lymphomalymphoma
22 . .Suppressor genesSuppressor genes
Genes involved in the recognition and repair of damaged DNAGenes involved in the recognition and repair of damaged DNA..
The loss of function of this genes cause inability of DNA repair The loss of function of this genes cause inability of DNA repair and lead to tumor formation ( mostly solid tumors )and lead to tumor formation ( mostly solid tumors ). .
The oncogenicity is derived from the loss of the gene rather than The oncogenicity is derived from the loss of the gene rather than activationactivation. .
Some S. genes found in human tumorsSome S. genes found in human tumors
genegenecancercancer
P53 P53 MUTATIONMUTATION
Breast , colorectal , lung , liver , renalBreast , colorectal , lung , liver , renal
BRCA1 BRCA1 MUTATIONMUTATION
Breast , melanomaBreast , melanoma
BRCA2 BRCA2 MUTATIONMUTATION
BreastBreast
RETMedullary thyroid cancer
Genetic Testing for CancerGenetic Testing for CancerSusceptibilitySusceptibility
Genetic testing should be carried outGenetic testing should be carried out::
# # If the individual has personal or family If the individual has personal or family historyhistory
suggestive of cancer susceptibilitysuggestive of cancer susceptibility
# # If the test can be adequately interpretedIf the test can be adequately interpreted
# # If the test will aid the diagnosis or influence If the test will aid the diagnosis or influence the medical or surgical management of the patient the medical or surgical management of the patient or family membersor family members
J Clin Oncol 2003;21:1J Clin Oncol 2003;21:1
How to identify tumor markerHow to identify tumor marker? ?
On cellOn cellCytochemistry, Flow cytometryCytochemistry, Flow cytometry
On tissueOn tissueHistochemistry, Cytosol assaysHistochemistry, Cytosol assays
In body fluidsIn body fluidsBlood, urine, CSF, Amniotic fluidBlood, urine, CSF, Amniotic fluid