MLAB 2401: CLINICAL CHEMISTRYKERI BROPHY-MARTINEZTumor 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 more than 50 tissues.

INTRODUCTION Cancer

Uncontrolled growth of cells that can develop into a solid 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 markers

CANCER AND DEATHS FROM CANCER IN USA

Male Female

Tissue Incidence Death

Tissue Incidence Death

Genital 30% 10% Breast 29% 14%

Respiratory 15% 30% Respiratory 14% 27%

Colorectal

10% 9% Colorectal

11% 10%

TERMS Tumorigenesis

Formation of tumors Occur due to mutation of growth factors and

oncogenes

Metastasis Spreading of tumors

Oncofetal Expressed during the development of the fetus,

then reexpressed in tumors

TERMS Sensitivity

The likelihood that given the presence of disease, an abnormal test result predicts the disease

No false negatives

Specificity The likelihood that given the absence of disease,

a normal test result excludes disease 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 concentrations

Tumor specific ( high specificity) absent in healthy individuals readily detectable in body fluids.

Unfortunately, all of the presently available tumor markers do not fit this ideal model.

APPLICATION OF TUMOR MARKERS Screening populations at risk

Not all tumor markers are good screening tools Diagnosis

Use results from markers, imaging, risk factors, and symptoms

Prognosis Concentration 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 Hook effect: excessive high marker concentrations

result in false lows Heterophile Antibodies

Interfere with testing due to the presence of circulating antibodies against animal immunoglobulin

Lipemia, hemolysis and antibody cross reactivity cause interferences

TUMOR MARKERS: ENZYMES Increase due to metabolic demands of cells Indicate tumor burden Examples

Alkaline phosphataseBone, liver, intestine

Creatine kinase Prostate, lung, breast, colon, ovarian

Lactate dehydrogenaseLiver, lymphomas, leukemias

Prostatic acid phosphataseProstate

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/ HORMONESDetect secreting tumorsHelpful in identification of:

NeuroblastomaPituitary tumorAdrenal tumor

ExamplesBeta-human chorionic gonadotropinCalcitoninAdrenocorticotropin hormone (ACTH)

TUMOR MARKERS: HORMONES Human Chorionic Gonadotropin (hCG)

Hormone normally secreted in the placenta to maintain pregnancy

Molecule consists of two subunits: alpha & beta Elevated in trophoblastic tumors,

choriocarcinoma and germ cell tumors of the ovary and testis

Most immunoassays detect either the subunits or the total molecule

TUMOR MARKERS: PROTEINS Used to monitor therapy Examples

Beta-2-Microglobulin Reflects cell turnover

Immunoglobulins

TUMOR MARKERS: ONCOFETAL ANTIGENS Considered normal in fetal development Become detectable in tumor formation Examples

Carcino-embryonic antigen(CEA) Alpha-fetoprotein

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(α) – 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 (testes, ovaries)

NOTABLE MENTIONS Breast cancer

CA 15-3 Monitoring

HER-2 Monitoring

CA 27.29 Monitoring

Ovarian cancer CA 125

Monitoring Pancreatic cancer

CA19-9 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 .