MLAB 2401: Clinical Chemistry Keri Brophy-Martinez

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MLAB 2401 Clinical ChemistryKeri Brophy-Martinez

• Tumor Markers

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Introduction

• Cancer is the second leading cause of death in
  North America, accounting for gt 2.7 million
  deaths annually.
• Although it is often specified as a single
  disorder, cancer is a broad term used to describe
  gt 200 different diseases that affect more than
  50 tissues.

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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

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Cancer and deaths from cancer in USA
Male Male Male Female Female 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
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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

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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

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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

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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.

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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

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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

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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

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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

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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)

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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

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Tumor markers proteins

• Used to monitor therapy
• Examples
• Beta-2-Microglobulin
• Reflects cell turnover
• Immunoglobulins

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Tumor markers oncofetal antigens

• Considered normal in fetal development
• Become detectable in tumor formation
• Examples
• Carcino-embryonic antigen(CEA)
• Alpha-fetoprotein

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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

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Frequently Ordered Tumor Markers

• Alpha(a) 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)

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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

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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
  .