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Category: Immunology
Immunoassay-Based Tumor Marker Measurement: Assays, Applications, and Algorithms, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818722/9781555818715_CH108-1.gif /docserver/preview/fulltext/10.1128/9781555818722/9781555818715_CH108-2.gifAbstract:
Tumor markers are molecules derived from patient body fluids or tissues that are measured and can provide information useful for the management of cancer patients. Applications include detection of cancer, monitoring of disease progression, and evaluation of the effectiveness of therapeutic regimens, among others. Henry Bence-Jones discovered the first tumor marker in 1846—a protein seen in acidified urine of patients with multiple myeloma (1). Since that time, many more tumor markers have been described for a variety of other cancers. The Food and Drug Administration (FDA) has approved several of these markers (Table 1), and many more are being investigated and evaluated for clinical use. The goal of this chapter is to review how tumor marker assays are evaluated, describe the applications of tumor markers, provide details on the detection of tumor markers using immunoassays, and then list examples of clinically useful tumor markers that are used in the clinical laboratory today. Although the last few years have witnessed a plethora of developments in molecular testing of tumor markers, these will not be discussed here, as we will restrict our discussion to immunoassay-based detection methods.
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(Left) Schematic diagram of a competitive binding (labeled-antigen) immunoassay. In this assay, a limited amount of immobilized antibody binds both labeled and unlabeled forms of the tumor marker antigen of interest. (Right) The higher the concentration of unlabeled tumor marker antigen in the subject's serum, the lower the signal generated by bound labeled antigen.
(Left) Schematic diagram of a competitive binding (labeled-antigen) immunoassay. In this assay, a limited amount of immobilized antibody binds both labeled and unlabeled forms of the tumor marker antigen of interest. (Right) The higher the concentration of unlabeled tumor marker antigen in the subject's serum, the lower the signal generated by bound labeled antigen.
Schematic diagram of a noncompetitive binding two-site sandwich immunometric (labeled-antibody) assay. In this assay, molar excess immobilized antibody specific for the tumor marker binds unlabeled forms of the tumor marker antigen in the patient's serum. Bound antigen is then detected with a second antitumor marker antibody that binds to a different antigenic epitope. Either the second antibody can be detected by a third labeled antibody (left) or the second antibody can be directly labeled (middle). The higher the concentration of unlabeled tumor marker antigen in the subject's serum, the higher the signal generated by bound detection antibody (right).
Schematic diagram of a noncompetitive binding two-site sandwich immunometric (labeled-antibody) assay. In this assay, molar excess immobilized antibody specific for the tumor marker binds unlabeled forms of the tumor marker antigen in the patient's serum. Bound antigen is then detected with a second antitumor marker antibody that binds to a different antigenic epitope. Either the second antibody can be detected by a third labeled antibody (left) or the second antibody can be directly labeled (middle). The higher the concentration of unlabeled tumor marker antigen in the subject's serum, the higher the signal generated by bound detection antibody (right).
In immunometric assays, a hook effect can occur when the capture and detection antibodies bind to different molecules, without the formation of a “sandwich,” as shown on the left panel. This results in an erroneous decrease in the measured signal at high concentrations of analyte; the effect on the dose-response curve is shown on the right panel.
In immunometric assays, a hook effect can occur when the capture and detection antibodies bind to different molecules, without the formation of a “sandwich,” as shown on the left panel. This results in an erroneous decrease in the measured signal at high concentrations of analyte; the effect on the dose-response curve is shown on the right panel.
Schematic diagram showing result deviation from linearity that may be caused by interference.
Schematic diagram showing result deviation from linearity that may be caused by interference.
FDA-approved tumor markers
FDA-approved tumor markers
Assay interferences that cause falsely elevated or decreased tumor marker results
Assay interferences that cause falsely elevated or decreased tumor marker results