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Chapter 131 : Immunologic Approaches to Tumor Markers: Assays, Applications, and Discovery

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Abstract:

This chapter reviews the design, performance, and application of tumor marker assays; interferences; specific tumor markers; and the impact of new technologies on the discovery of novel tumor markers. In most populations, there is an overlap between the noncancer and cancer groups, since individuals without cancer may exhibit elevated levels of a marker and some individuals with cancer may not show elevations in a particular marker. The possible applications for tumor markers include screening, diagnosis, monitoring of therapy, detection of disease recurrence, and determination of prognosis. The prevalence of most cancers in the population is low, but with the inappropriate sensitivity and specificity of some tumor marker assays, false-positive results may be generated. Surgical removal of the tumor should result in a dramatic fall of the tumor marker, consistent with its half-life. Antibodies can be employed for specific targeting of analytes in many complex biological matrices, including blood (whole or a portion thereof), urine, and other fluids. The specificity of the antigen-antibody interaction, coupled with the exquisite sensitivity of enhanced signal detection methods available today, makes immunoassays the method of choice in laboratory medicine.

Citation: Rai A, Chan D. 2006. Immunologic Approaches to Tumor Markers: Assays, Applications, and Discovery, p 1145-1151. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch131

Key Concept Ranking

Sandwich Enzyme-Linked Immunosorbent Assay
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Figures

Image of FIGURE 1
FIGURE 1

Competitive assay format. In this format, a labeled antigen is added in the presence of antigen from the sample. A competition is established, resulting in an inverse relationship between the sample concentration and the assay signal.

Citation: Rai A, Chan D. 2006. Immunologic Approaches to Tumor Markers: Assays, Applications, and Discovery, p 1145-1151. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch131
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Image of FIGURE 2
FIGURE 2

Sandwich enzyme-linked immunosorbent assay (ELISA) format. There are two alternatives for this design, as shown in the figure. In panel A, the analyte is sandwiched by the capture and detection antibodies, and a third antibody coupled to a signal molecule is added. An example of this format would be the use of two antibodies from two different species and a third universal reagent. In panel B, the detection antibody is directly coupled to the signal molecule; when it forms the sandwich, it can generate signal for quantification. An example of this format would be a custom antibody coupled to horseradish peroxidase.

Citation: Rai A, Chan D. 2006. Immunologic Approaches to Tumor Markers: Assays, Applications, and Discovery, p 1145-1151. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch131
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Image of FIGURE 3
FIGURE 3

Hook effect. Excess analyte results in the binding of both antibodies, but no signal is generated.

Citation: Rai A, Chan D. 2006. Immunologic Approaches to Tumor Markers: Assays, Applications, and Discovery, p 1145-1151. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch131
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References

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1. Chan, D. W. (ed.). 1987. Immunoassay: a Practical Guide. Academic Press Inc., San Diego, Calif.
2. Chan, D. W., and , M. K. Schwartz. 2002. Tumor markers: introduction and general principles, p. 918. In E. P Diamandis,, H. A. Fritsche,, H. Lilja,, D. W. Chan, and , M. K. Schwartz (ed.), Tumor Markers: Physiology, Patho-biology, Technology, and Clinical Applications. AACC Press, Washington, D.C.
3. Diamandis, E. P. 2002. Tumor markers: past, present, and future, p. 38. In E. P. Diamandis,, H. A. Fritsche,, H. Lilja,, D. W. Chan, and , M. K. Schwartz (ed.), Tumor Markers: Physiology, Pathobiology, Technology, and Clinical Applications. AACC Press, Washington, D.C.
4. Gold, P., and , S. O. Freedman. 1965. Demonstration of tumor specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J. Exp. Med. 121:439462.
5. Jung, K.,, J. Reiche,, A. Boehme,, C. Stephan,, S. A. Loening,, D. Schnorr,, W. Hoesel, and , F. Sinha. 2004. Analysis of subforms of free prostate-specific antigen in serum by two-dimensional gel electrophoresis: potential to improve diagnosis of prostate cancer. Clin. Chem. 50:22922301.
6. Lilja, H. 2003. Biology of prostate-specific antigen. Urology 62(Suppl. 5A):2733.
7. Rai, A. J., and , D. W. Chan. 2004. Cancer proteomics: serum diagnostics for tumor marker discovery. Ann. N. Y Acad. Sci. 1022:286294.
8. Solberg, H. E. 2001. Establishment and use of reference values, p. 251261. In C. A. Burtis and , E. R. Ashwood (ed.), Tietz Fundamentals of Clinical Chemistry. W. B. Saunders, Philadelphia, Pa.
9. Sturgeon, C. M. 2002. Limitations of assay techniques for tumor markers, p. 6581. In E. P. Diamandis,, H. A. Fritsche,, H. Lilja,, D. W. Chan, and , M. K. Schwartz (ed.), Tumor Markers: Physiology, Pathobiology, Technology and Clinical Applications. AACC Press, Washington, D.C.
10. Wu, J. T. 2000. Quantitative Immunoassay: a Practical Guide for Assay Establishment, Troubleshooting, and Clinical Application. AACC Press, Washington, D.C.
11. Zhang, Z. 2002. Combining multiple markers in clinical diagnostics: a review of methods and issues, p. 133140. In E. P. Diamandis,, H. A. Fritsche,, H. Lilja,, D. W Chan, and , M. K. Schwartz (ed.), Tumor Markers: Physiology, Pathobiology, Technology, and Clinical Applications. AACC Press, Washington, D.C.
12. Zweig, M. H., and , G. Campbell. 1993. Receiver operating characteristic plots: a fundamental tool in clinical medicine. Clin. Chem. 39:561577.

Tables

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TABLE 1

Food and Drug Administration-approved tumor marker tests

Citation: Rai A, Chan D. 2006. Immunologic Approaches to Tumor Markers: Assays, Applications, and Discovery, p 1145-1151. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch131

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