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Clinical Chemistry, Vol 39, 2483-2491, Copyright © 1993 by American Association for Clinical Chemistry
AM Zhou, PC Tewari, BI Bluestein, GW Caldwell and FL Larsen
Oncology Programs, Cancer Care Diagnostics Product Development, Ciba Corning Diagnostics Corp., East Walpole, MA 02032.
Prostate-specific antigen (PSA) in serum is primarily complexed with alpha 1-antichymotrypsin (alpha 1-ACT). However, 12-15% of prostate cancer (PCa) patients present with the predominant form being uncomplexed (free) PSA (Lilja et al., Clin Chem 1991;37:1618-24). We report that commercial immunoassays demonstrate variations in reactivity, especially to the uncomplexed form. We fractionated and analyzed commercial controls, PSA complexes prepared in vitro, and sera from patients with PCa or benign prostatic hyperplasia, using molecular sieve chromatography and Hybritech Tandem-R, Abbott IMx, and Ciba Corning ACS PSA assays. Peak integration of PCa samples demonstrated ACS:Tandem-R ratios of 1-1.3 for PSA/alpha 1-ACT complex. In contrast, ratios of uncomplexed peaks ranged from 2 to 4, suggesting a greater reactivity of the uncomplexed form in the ACS PSA assay. Discrepancies between assays, when PSA was measured in unfractionated sera, correlated directly with the percentage of the uncomplexed form. In controls, fractionation revealed the presence of uncomplexed PSA only, with ratios of ACS:Tandem-R and IMx:Tandem-R of 3:1 and 1.8:1, respectively. Immunoblots of PCa sera detected uncomplexed PSA (approximately 30 kDa) and PSA complexes of approximately 95 kDa (PSA/alpha 1-ACT) and > 200 kDa, indicative of alpha 2-macroglobulin. Maximal recognition of all forms of PSA may be important for early detection of disease progression.
The following articles in journals at HighWire Press have cited this article:
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A. Semjonow, F. Oberpenning, C. Weining, M. Schon, B. Brandt, G. De Angelis, A. Heinecke, M. Hamm, P. Stieber, L. Hertle, et al. Do Modifications of Nonequimolar Assays for Total Prostate-specific Antigen Improve Detection of Prostate Cancer? Clin. Chem., August 1, 2001; 47(8): 1472 - 1475. [Full Text] [PDF]
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H. Nagasaki, M. Watanabe, N. Komatsu, T. Kaneko, J. Y. Dube, T. Kajita, Y. Saitoh, and Y. Ohta Epitope Analysis of a Prostate-specific Antigen (PSA) C-Terminal-specific Monoclonal Antibody and New Aspects for the Discrepancy between Equimolar and Skewed PSA Assays Clin. Chem., April 1, 1999; 45(4): 486 - 496. [Abstract] [Full Text] [PDF]
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C. D. Cheli, M. Marcus, J. Levine, Z. Zhou, P. H. Anderson, D. D. Bankson, J. Bock, S. Bodin, C. Eisen, M. Senior, et al. Variation in the Quantitation of Prostate-specific Antigen in Reference Material: Differences in Commercial Immunoassays, Clin. Chem., July 1, 1998; 44(7): 1551 - 1553. [Full Text] [PDF]
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P. C. Tewari, J. S. Williams, A. B. Blase, and R. L. Sokoloff Analytical Characteristics of Seminal Fluid PSA Differ from Those of Serum PSA Clin. Chem., January 1, 1998; 44(1): 191 - 193. [Full Text] [PDF]
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A. B. Blase, R. L. Sokoloff, and K. M. Smith Five PSA Methods Compared by Assaying Samples with Defined PSA Ratios, Clin. Chem., May 1, 1997; 43(5): 843 - 845. [Full Text]
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