MLAB 2401: CLINICAL
CHEMISTRY
KERI BROPHY-MARTINEZ
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.
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%
9%
Colorectal 11%
10%
Colorectal 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


Diagnosis


Concentration of the marker determines prognosis
Detection of recurrence


Use results from markers, imaging, risk factors, and
symptoms
Prognosis


Not all tumor markers are good screening tools
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


Creatine kinase


Prostate, lung, breast, colon, ovarian
Lactate dehydrogenase


Bone, liver, intestine
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
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


HER-2


Monitoring
Ovarian cancer

CA 125


Monitoring
CA 27.29


Monitoring
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 .