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 more than 50 tissues.
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
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
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

COMMON CANCER TERMS
Angiogenesis: development of new blood vessels to supply oxygen and nutrients to cells
Apoptosis: programmed cell death
Cell cycle: phases of cell activity divided into G, S, and M (growth, DNA synthesis, and mitosis, respectively)
Oncogene: encodes a protein that, when mutated, promotes uncontrolled cell growth
Tumor suppressor gene: encodes a protein involved in protecting cells from unregulated growth

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 phosphatase
Bone, liver, intestine
Creatine kinase
Prostate, 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
Calcitonin
Adrenocorticotropin 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
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 (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