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

1. Tumor Markers 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 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. • 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 )

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 ScreeningTests

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

9. Disease Management • Most TM are usedto 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.

10. Enzymes & Isoenzymes

11. Hormones

12. Oncofetal Ags :Normally produced proteins during fetal life, decrease to low levels or disappear after birth and reappear in cancer patients

13. Carbohydrate markers: Either are antigens on the tumor cell surface or are secreted by the tumor cellsThey are high molecular weight mucins or blood group antigens

14. Proteins TM

15. Other tumor markers

16. Genetic Markers • Two 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

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

20. Genetic Testing for CancerSusceptibility 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 ClinOncol 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

23. Thank you