Presentation on theme: "Dr. Amal S. Ahmed Ass Prof.Clinical Pathology Suez Canal University"— Presentation transcript:
1Dr. Amal S. Ahmed Ass Prof.Clinical Pathology Suez Canal University Tumor MarkersDr. Amal S. AhmedAss Prof.Clinical PathologySuez Canal University
2Historical background of tumor markers The first TM reported was Bence Jones protein. Since its discovery in 1847 by precipitation of a protein in acidified boiled urine , the measurement of B.J.P has been a diagnostic test for Multiple myloma (plasma cell tumor).The general application of TM for monitoring cancer patient start with the discovery of AFP in 1963 and CEA in 1965.
3Definition of TMA substance produced or induced by tumor cells and released into blood , body fluids or expressed on cell surface , that can be used to differentiate a tumor from normal tissue or to determine the presence of a tumor.Few markers are specific for a single individual tumor( tumor-specific markers )Most are found with different tumors of the same tissue type(tumor-associated markers )
4Classification of TM Enzymes & isoenzymes Hormones Oncofetal antigens Carbohydrates markersProteinsReceptors & other markersGenetic markers(Oncogenes & suppressor gene mutations )
5Potential uses of TM Screening in general population Clinical staging of cancerPrognostic indicator for disease progressEvaluation of treatment successDetection the recurrence of cancerMonitoring response to therapyRadioimmunolocalization of tumor
6Recommended Cancer Screening Tests TechniqueCancerMammographyBreastSigmoidoscopyCRCAPAPCervicalVMANeuroblastomaAFPHCCPSAProstateCA 125Ovarian
7Predictive MarkersER and PR: For predicting response to hormone therapy in breast cancer HER-2: For predicting response to trastuzumab (Herceptin) in breast cancer
9Disease ManagementMost TM are used to monitor treatment and progression of cancer .Single determination does not allow definite conclusion.Combining different markers can improve the diagnostic precision.Normal level ( negative result ) does not exclude malignancy.
12Oncofetal Ags :Normally produced proteins during fetal life, decrease to low levels or disappear after birth and reappear in cancer patientscancerTMHCC, germ cell carcinomaAFPColorectal, GIT, pancreas, lung, breastCEALiverCarcinofetal ferritinCervix, lung, skin, head & neckSquamous cell Ag
13Pancreatic , gastrointestinal , hepatic CA 19-9 Carbohydrate markers: Either are antigens on the tumor cell surface or are secreted by the tumor cells They are high molecular weight mucins or blood group antigenscancerTMOvarian , endometrialCA 125Breast , ovarianCA 15-3Pancreatic , gastrointestinal , hepaticCA 19-9Gastrointestinal , Pancreatic , ovarianCA 19-5Pancreatic , gastrointestinal , colonCA 50
14Proteins TM cancer MM ,B-cell lymphoma ,CLL B2-microglobulin InsulinomaC-peptideLiver, lung, breast, leukemiaFerritinMM , lymphomasimmunoglobulin
15Other tumor markers Cancer Nature TM Breast Tissue Estrogen & progesterone receptorsNuroblastoma , phyochromocytomaUrine ( VMA , HVA )Catecholamine metabolitesBone metastasis (breast) , MMUrineHydroxypoline
16Genetic MarkersTwo classes of genes are involved in the development of cancer :Oncogens :cell activation genes that code for products involved in normal cellular processes such as growth factor signaling pathways.over expression ( activation ) of oncogens will lead to abnormal cell growth , resulting in malignancy (mostly hematological malignancy ).
17Some oncogens found in human tumors cancerfunctiononcogenAML, nuroblastomaSignal transductionN-ras mutationLeukemia, lymphomaK-ras mutationBlocks apoptosisbcl-2
182. Suppressor genesGenes involved in the recognition and repair of damaged DNA.The loss of function of this genes cause inability of DNA repair and lead to tumor formation ( mostly solid tumors ) .The oncogenicity is derived from the loss of the gene rather than activation .
19Some S. genes found in human tumors cancergeneBreast , colorectal , lung , liver , renalP53 MUTATIONBreast , melanomaBRCA1 MUTATIONBreastBRCA2 MUTATIONMedullary thyroid cancerRET
20Genetic Testing for Cancer Susceptibility Genetic testing should be carried out: # If the individual has personal or family history suggestive of cancer susceptibility # If the test can be adequately interpreted # If the test will aid the diagnosis or influence the medical or surgical management of the patient or family members J Clin Oncol 2003;21:1
21How to identify tumor marker ? On cellCytochemistry, Flow cytometryOn tissueHistochemistry, Cytosol assaysIn body fluidsBlood, urine, CSF, Amniotic fluid