1. Unit 6: Tumor markers

2. Introduction… Cancer is the second leading cause of death in North America, accounting for > 2.7 million deaths annually Although it is often specified as a single disorder, cancer is a broad term used to describe > 200 different diseases that affect > 5o tissues

3. Cancer… Uncontrolled growth of cells that can develop into a solid tissue mass or tumor and spread to other areas of the body Severity is classified by tumor size, histology, regional lymph node involvement and presence of metastasis Detected and monitored by ______tumor maker__________

5. terms Tumorigenesis …formation of tumor …occur due to mutation of growth factors and oncogenes Metastasis …spreading of tumors oncofetal …expressed during the development of the fetus, then re-expressed in tumors

6. Terms cont’d… Sensitivity …the likelihood that given the : presence of diseases, an abnormal test result predicts the diseases …no false negative specificity …the likelihood that given the: absence of diseases, a normal test result excludes diseases …no false positives

7. What is a tumor marker? Produced directly by the tumor or as an effect of the tumor on healthy tissue Concentration increases with tumor progression, highest levels when tumors metastasize Include diverse molecules such as serum proteins, oncofetal antigens, hormones, metabolites, receptors, and enzymes

8. Tumor marker detection Ideally, a tumor marker would be: …a substance that is: released directly into the bloodstream detectable at small concentration …absent in healthy individuals …tumor specific (high specificity) …readily detectable in body fluids unfortunately, all of the presently available tumor markers do not fit this ideal model

9. Application of tumor markers Screening population at risk …not all tumor markers are good screening tools diagnosis …use results from markers, imaging, risk factors, and symptoms prognosis …concentrations of the marker determines prognosis detection of recurrence …once tumor is removed, elevations of marker can indicate regrowth monitoring response to treatment …decreased levels of tumor marker indicate therapy is working …increased levels of tumor marker may indicate need for a change to therapy

10. Methods for detection Immunoassay …most common measurement method …challenges …markers often above linearity (must dilute) …hook effect: excessive high [maker] result in false low …heterophile antibodies …interfere with testing due to the presence of antibodies against animal immunoglobulin …lipemia, hemolysis, and cross reactivity cause interferences

11. Tumor markers: enzymes Increase due metabolic demands of cells Indicate Examples: …alkaline phosphatase (bone, liver, intestine) … creatine kinase(prostrate, lung, breast, colon, ovarian) … lactate dehydrogenase(liver, lymphomas, leukemias) … prostatic acid phosphatase(prostate)

12. Frequently ordered tumor markers prostate specific antigen (PSA) …produced in the epithelial cells of the prostatic ducts …consists of two forms: free and complexed …in healthy men, some amounts of psa can be detected …psa is elevated in prostate infection, irritation and benign Prostate enlargement …methodology detects both forms

13. Tumor markers: endocrine/hormones Detect : secreting tumors Helpful in identification of: …neuroblastoma …pituitary tumor …adrenal tumor Examples: …beta-human chorionic gonadotropin (B-HCG) …calutonin …adrenocorticotropin hormone (ACTH)

14. Tumor markers: hormones Human chorionic gonadotropin (HCG) …molecule consists of two subunits: alpha and beta …elevated in trophoblastic tumors, choriocarcinoma, and germ cell tumors of the ovaries and testes …most immunoassays detect either the subunits or the total molecule

15. Tumor markers: proteins Used to monitor therapy Examples: -Beta-2-macroglobulin -reflects cell turnover immunoglobulins

16. Tumor markers: oncofetal antigens Considered : normal in fetal development Become detectable : in tumor formation Examples: - garcino-embryonic antigen (CEA) - alpha-fetoprotein (AFP)

17. Frequently ordered tumor markers Carcinoembryonic antigen (CEA) …expressed during fetal development then re-expressed in tumor growth …clinical use: -used to detect colorectal, lung, breast, ovarian and GI cancers -monitor therapy

18. Frequently ordered tumor markers alpha-fetoprotein (AFP) …synthesized by the fetal liver …re-expresses in certain types of tumors …normally functions as a transport protein and helps to regulate oncotic pressure in the fetus …used to diagnose hepatocellular carcinoma and germ cell tumors (ovaries and testes)

19. Notable mentions Breast cancer …CA-15-3 (monitoring) …HER-2 (monitoring) …CA-27,29 (monitoring) ovarian cancer …CA 125 (monitoring) Pancreatic cancer …CA 19-9 (monitoring)

22. References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins Rhea, J. M., & Molinaro, R. J. (2011, March). Cancer Biomarkers: Surviving the Journey From Bench to Bedside. MLO, 43(3), 10-18. Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson.