Presentation on theme: "Dr. Amal S. Ahmed Ass Prof.Clinical Pathology Suez Canal University"— Presentation transcript:
1 Dr. Amal S. Ahmed Ass Prof.Clinical Pathology Suez Canal University Tumor MarkersDr. Amal S. AhmedAss Prof.Clinical PathologySuez Canal University
2 Historical 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.
3 Definition 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 )
5 Potential 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
6 Recommended Cancer Screening Tests TechniqueCancerMammographyBreastSigmoidoscopyCRCAPAPCervicalVMANeuroblastomaAFPHCCPSAProstateCA 125Ovarian
7 Predictive MarkersER and PR: For predicting response to hormone therapy in breast cancer HER-2: For predicting response to trastuzumab (Herceptin) in breast cancer
9 Disease 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.
12 Oncofetal 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
13 Pancreatic , 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
14 Proteins TM cancer MM ,B-cell lymphoma ,CLL B2-microglobulin InsulinomaC-peptideLiver, lung, breast, leukemiaFerritinMM , lymphomasimmunoglobulin
15 Other tumor markers Cancer Nature TM Breast Tissue Estrogen & progesterone receptorsNuroblastoma , phyochromocytomaUrine ( VMA , HVA )Catecholamine metabolitesBone metastasis (breast) , MMUrineHydroxypoline
16 Genetic 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 ).
17 Some oncogens found in human tumors cancerfunctiononcogenAML, nuroblastomaSignal transductionN-ras mutationLeukemia, lymphomaK-ras mutationBlocks apoptosisbcl-2
18 2. 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 .
19 Some S. genes found in human tumors cancergeneBreast , colorectal , lung , liver , renalP53 MUTATIONBreast , melanomaBRCA1 MUTATIONBreastBRCA2 MUTATIONMedullary thyroid cancerRET
20 Genetic 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
21 How to identify tumor marker ? On cellCytochemistry, Flow cytometryOn tissueHistochemistry, Cytosol assaysIn body fluidsBlood, urine, CSF, Amniotic fluid