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Dr. Amal S. Ahmed Ass Prof.Clinical Pathology Suez Canal University.

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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

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 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 The general application of TM for monitoring cancer patient start with the discovery of AFP in 1963 and CEA in 1965.

3 Definition of TM A 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. A 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 Few markers are specific for a single individual tumor ( tumor-specific markers ) ( tumor-specific markers ) Most are found with different tumors of the same tissue type Most are found with different tumors of the same tissue type (tumor-associated markers ) (tumor-associated markers )

4 Classification of TM Enzymes & isoenzymes Hormones Oncofetal antigens Carbohydrates markers Proteins Receptors & other markers Genetic markers (Oncogenes & suppressor gene mutations )

5 Potential 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

6 Recommended Cancer Screening Tests TechniqueCancer MammographyBreast SigmoidoscopyCRCA PAPCervical VMANeuroblastoma AFP HCC PSA Prostate CA 125 Ovarian

7 Predictive Markers ER and PR: For predicting response to hormone therapy in breast cancer hormone therapy in breast cancer HER-2: For predicting response to trastuzumab (Herceptin) in breast cancer trastuzumab (Herceptin) in breast cancer

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9 Disease Management Most TM are used to monitor treatment and progression of cancer. Most TM are used to monitor treatment and progression of cancer. Single determination does not allow definite conclusion. Single determination does not allow definite conclusion. Combining different markers can improve the diagnostic precision. Combining different markers can improve the diagnostic precision. Normal level ( negative result ) does not exclude malignancy. Normal level ( negative result ) does not exclude malignancy.

10 Enzymes & Isoenzymes cancerTM LiverAldolase PancreaticAmylase Liver, Bone, leukemia & lymphoma Alp Prostate, lung, breast, colon, ovary CK-BB Liver, leukemia & lymphoma LDH LiverGGT ProstatePSA&PAP breastElastase

11 Hormones cancerTM Cushing s & Lung ACTH Lung, adrenal cortex, pancreas ADH Liver, renal, breast, lung PTH Medullary thyroid Calcitonin GlucagonomaGastrin Pituitary, renal, lung GH choriocarcinomahCG Prolactin

12 Oncofetal Ags : Oncofetal Ags :Normally produced proteins during fetal life, decrease to low levels or disappear after birth and reappear in cancer patients cancerTM HCC, germ cell carcinoma AFP Colorectal, GIT, pancreas, lung, breast CEA Liver Carcinofetal ferritin Cervix, lung, skin, head & neck Squamous cell Ag

13 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 antigens 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 antigens cancerTM Ovarian, endometrial CA 125 Breast, ovarian CA 15-3 Pancreatic, gastrointestinal, hepatic CA 19-9 Gastrointestinal, Pancreatic, ovarian CA 19-5 Pancreatic, gastrointestinal, colon CA 50

14 Proteins TM cancerTM MM,B-cell lymphoma,CLL B 2-microglobulin InsulinomaC-peptide Liver, lung, breast, leukemia Ferritin MM, lymphomas immunoglobulin

15 Other tumor markers CancerNatureTM BreastTissue Estrogen & progesterone receptors Nuroblastoma, phyochromocytoma Urine ( VMA, HVA ) Catecholamine metabolites Bone metastasis (breast), MM UrineHydroxypoline

16 Genetic Markers Two classes of genes are involved in the development of cancer : Two classes of genes are involved in the development of cancer : 1. Oncogens : cell activation genes that code for products involved in normal cellular processes such as growth factor signaling pathways. 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 ). over expression ( activation ) of oncogens will lead to abnormal cell growth, resulting in malignancy (mostly hematological malignancy ).

17 Some oncogens found in human tumors cancerfunctiononcogen AML, nuroblastoma Signal transduction N-ras mutation Leukemia, lymphoma Signal transduction K-ras mutation Leukemia, lymphoma Blocks apoptosis bcl-2

18 2. Suppressor genes Genes 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 cancergene Breast, colorectal, lung, liver, renal P53 MUTATION Breast, melanoma BRCA1 MUTATION Breast BRCA2 MUTATION Medullary thyroid cancerRET

20 Genetic Testing for Cancer Susceptibility Genetic Testing for Cancer Susceptibility Genetic testing should be carried out: # If the individual has personal or family history # If the individual has personal or family history suggestive of cancer susceptibility # If the test can be adequately interpreted # 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 # 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 cell Cytochemistry, Flow cytometry On tissue Histochemistry, Cytosol assays In body fluids Blood, urine, CSF, Amniotic fluid

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