Unit 6: Tumor markers
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
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__________
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
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
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
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
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
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
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)
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
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)
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
Tumor markers: proteins
• Used to monitor therapy
• Examples:
-Beta-2-macroglobulin
-reflects cell turnover immunoglobulins
Tumor markers: oncofetal antigens
• Considered : normal in fetal development
• Become detectable : in tumor formation
• Examples:
- garcino-embryonic antigen (CEA)
- alpha-fetoprotein (AFP)
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
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)
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)
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 .