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Clinical Chemistry, Vol 42, 675-684, Copyright © 1996 by American Association for Clinical Chemistry
RA Ferguson, H Yu, M Kalyvas, S Zammit and EP Diamandis
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
We report an ultrasensitive time-resolved immunofluorometric assay (TRIFA) for prostate-specific antigen (PSA). The assay is an improvement of our previous report (Clin Chem 1993;39:2108-14) and includes the utilization of two monoclonal antibodies and a one-step incubation period, which greatly reduces analysis time. The new method demonstrates a superior lower analytical limit of detection (< or = 1 ng/L), a wide dynamic range, absence of a hook effect at 10(6) ng/L PSA, and equimolarity for free PSA and PSA-antichymotrypsin complex. Also, we have compared several aspects of our TRIFA with a commercially available third-generation assay (Immulite). An evaluation of breast tumor cytosol extracts from 315 patients shows PSA immunoreactivity > 15 ng/g of total protein in 28% and 23% by TRIFA and Immulite analysis, respectively. Both methods demonstrate a significant association between breast tumor PSA immunoreactivity and progesterone and estrogen receptor positivity (P <0.001). Analysis of serum samples obtained for monitoring of postradical prostatectomy patients reveals significant PSA changes at concentrations undetectable by conventional methods. The significance of these results as well as the potential applications of ultrasensitive PSA assays in breast and prostate cancers are discussed.
The following articles in journals at HighWire Press have cited this article:
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  X. Dong, J. Sweet, J. R. G. Challis, T. Brown, and S. J. Lye Transcriptional Activity of Androgen Receptor Is Modulated by Two RNA Splicing Factors, PSF and p54nrb Mol. Cell. Biol., July 1, 2007; 27(13): 4863 - 4875. [Abstract] [Full Text] [PDF]
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 M. H. Slagter, A. Scorilas, L. J.G. Gooren, W. de Ronde, A. Soosaipillai, E. J. Giltay, M. Paliouras, and E. P. Diamandis Effect of Testosterone Administration on Serum and Urine Kallikrein Concentrations in Female-to-Male Transsexuals Clin. Chem., August 1, 2006; 52(8): 1546 - 1551. [Abstract] [Full Text] [PDF]
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M. H. Slagter, L. J.G. Gooren, W. de Ronde, A. Soosaipillai, A. Scorilas, E. J. Giltay, M. Paliouras, and E. P. Diamandis Serum and Urine Tissue Kallikrein Concentrations in Male-to-Female Transsexuals Treated with Antiandrogens and Estrogens Clin. Chem., July 1, 2006; 52(7): 1356 - 1365. [Abstract] [Full Text] [PDF]
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 K. A. Shaikh, K. S. Ryu, E. D. Goluch, J.-M. Nam, J. Liu, C. S. Thaxton, T. N. Chiesl, A. E. Barron, Y. Lu, C. A. Mirkin, et al. A modular microfluidic architecture for integrated biochemical analysis PNAS, July 12, 2005; 102(28): 9745 - 9750. [Abstract] [Full Text] [PDF]
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R. Rej Clinical Chemistry through Clinical Chemistry: A Journal Timeline Clin. Chem., December 1, 2004; 50(12): 2415 - 2458. [Abstract] [Full Text] [PDF]
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 C. A. Borgono, L. Grass, A. Soosaipillai, G. M. Yousef, C. D. Petraki, D. H. C. Howarth, S. Fracchioli, D. Katsaros, and E. P. Diamandis Human Kallikrein 14: A New Potential Biomarker for Ovarian and Breast Cancer Cancer Res., December 15, 2003; 63(24): 9032 - 9041. [Abstract] [Full Text] [PDF]
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 J.-M. Nam, C. S. Thaxton, and C. A. Mirkin Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins Science, September 26, 2003; 301(5641): 1884 - 1886. [Abstract] [Full Text] [PDF]
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T. Kishi, L. Grass, A. Soosaipillai, C. Shimizu-Okabe, and E. P. Diamandis Human Kallikrein 8: Immunoassay Development and Identification in Tissue Extracts and Biological Fluids Clin. Chem., January 1, 2003; 49(1): 87 - 96. [Abstract] [Full Text] [PDF]
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C. V. Obiezu, A. Soosaipillai, K. Jung, C. Stephan, A. Scorilas, D. H. C. Howarth, and E. P. Diamandis Detection of Human Kallikrein 4 in Healthy and Cancerous Prostatic Tissues by Immunofluorometry and Immunohistochemistry Clin. Chem., August 1, 2002; 48(8): 1232 - 1240. [Abstract] [Full Text] [PDF]
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B. R. Grzeda, T. Le Bui, C. N. Warner, T. L. Pirucki, L. M. Dewey, M. Babich, and J. A. Maggiore Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System Clin. Chem., August 1, 2002; 48(8): 1272 - 1278. [Abstract] [Full Text] [PDF]
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E. P. Diamandis, A. Okui, S. Mitsui, L.-Y. Luo, A. Soosaipillai, L. Grass, T. Nakamura, D. J. C. Howarth, and N. Yamaguchi Human Kallikrein 11: A New Biomarker of Prostate and Ovarian Carcinoma Cancer Res., January 1, 2002; 62(1): 295 - 300. [Abstract] [Full Text] [PDF]
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T. Soukka, J. Paukkunen, H. Harma, S. Lonnberg, H. Lindroos, and T. Lovgren Supersensitive Time-resolved Immunofluorometric Assay of Free Prostate-specific Antigen with Nanoparticle Label Technology Clin. Chem., July 1, 2001; 47(7): 1269 - 1278. [Abstract] [Full Text] [PDF]
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 G. M. Yousef and E. P. Diamandis The New Human Tissue Kallikrein Gene Family: Structure, Function, and Association to Disease Endocr. Rev., April 1, 2001; 22(2): 184 - 204. [Abstract] [Full Text]
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 C. V. Obiezu, A. Scorilas, A. Magklara, M. H. Thornton, C. Y. Wang, F. Z. Stanczyk, and E. P. Diamandis Prostate-Specific Antigen and Human Glandular Kallikrein 2 Are Markedly Elevated in Urine of Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1558 - 1561. [Abstract] [Full Text]
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E. P. Diamandis Signal Amplification in Time-resolved Fluorometry Clin. Chem., March 1, 2001; 47(3): 380 - 381. [Full Text] [PDF]
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H. Harma, T. Soukka, and T. Lovgren Europium Nanoparticles and Time-resolved Fluorescence for Ultrasensitive Detection of Prostate-specific Antigen Clin. Chem., March 1, 2001; 47(3): 561 - 568. [Abstract] [Full Text] [PDF]
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L.-Y. Luo, L. Grass, D. J.C. Howarth, P. Thibault, H. Ong, and E. P. Diamandis Immunofluorometric Assay of Human Kallikrein 10 and Its Identification in Biological Fluids and Tissues Clin. Chem., February 1, 2001; 47(2): 237 - 246. [Abstract] [Full Text] [PDF]
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A. Scorilas, A. Bjartell, H. Lilja, C. Moller, and E. P. Diamandis Streptavidin-Polyvinylamine Conjugates Labeled with a Europium Chelate: Applications in Immunoassay, Immunohistochemistry, and Microarrays Clin. Chem., September 1, 2000; 46(9): 1450 - 1455. [Abstract] [Full Text] [PDF]
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H. F. Escobar-Morreale, S. Ávila, and J. Sancho Serum Prostate-Specific Antigen Concentrations Are Not Useful for Monitoring the Treatment of Hirsutism with Oral Contraceptive Pills J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2488 - 2492. [Abstract] [Full Text]
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C. V. Obiezu, E. J. Giltay, A. Magklara, A. Scorilas, L. J.G. Gooren, H. Yu, D. J.C. Howarth, and E. P. Diamandis Serum and Urinary Prostate-specific Antigen and Urinary Human Glandular Kallikrein Concentrations Are Significantly Increased after Testosterone Administration in Female-to-Male Transsexuals Clin. Chem., June 1, 2000; 46(6): 859 - 862. [Abstract] [Full Text] [PDF]
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 B. Bharaj, A. Scorilas, M. Giai, and E. P. Diamandis TA Repeat Polymorphism of the 5{{alpha}}-Reductase Gene and Breast Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2000; 9(4): 387 - 393. [Abstract] [Full Text]
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 M. H. Black, M. Giai, R. Ponzone, P. Sismondi, H. Yu, and E. P. Diamandis Serum Total and Free Prostate-specific Antigen for Breast Cancer Diagnosis in Women Clin. Cancer Res., February 1, 2000; 6(2): 467 - 473. [Abstract] [Full Text]
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 N. L. Simone, A. T. Remaley, L. Charboneau, E. F. Petricoin III, J. W. Glickman, M. R. Emmert-Buck, T. A. Fleisher, and L. A. Liotta Sensitive Immunoassay of Tissue Cell Proteins Procured by Laser Capture Microdissection Am. J. Pathol., February 1, 2000; 156(2): 445 - 452. [Abstract] [Full Text] [PDF]
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A. Magklara, A. Scorilas, C. Lopez-Otin, F. Vizoso, A. Ruibal, and E. P. Diamandis Human Glandular Kallikrein in Breast Milk, Amniotic Fluid, and Breast Cyst Fluid Clin. Chem., October 1, 1999; 45(10): 1774 - 1780. [Abstract] [Full Text] [PDF]
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M. H. Black, A. Magklara, C. V. Obiezu, D. N. Melegos, and E. P. Diamandis Development of an Ultrasensitive Immunoassay for Human Glandular Kallikrein with No Cross-Reactivity from Prostate-specific Antigen Clin. Chem., June 1, 1999; 45(6): 790 - 799. [Abstract] [Full Text] [PDF]
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 D. J. Jenkins, C. W. Kendall, E. Vidgen, S. Agarwal, A V. Rao, R. S Rosenberg, E. P Diamandis, R. Novokmet, C. C Mehling, T. Perera, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial Am. J. Clinical Nutrition, March 1, 1999; 69(3): 395 - 402. [Abstract] [Full Text] [PDF]
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M. H. Black, C. L. Grass, J. Leinonen, U.-H. Stenman, and E. P. Diamandis Characterization of Monoclonal Antibodies for Prostate-specific Antigen and Development of Highly Sensitive Free Prostate-specific Antigen Assays Clin. Chem., March 1, 1999; 45(3): 347 - 354. [Abstract] [Full Text] [PDF]
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K. Spencer and P. Carpenter Is Prostate-specific Antigen a Marker for Pregnancies Affected by Down Syndrome? Clin. Chem., November 1, 1998; 44(11): 2362 - 2365. [Full Text] [PDF]
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C. Lopez-Otin and E. P. Diamandis Breast and Prostate Cancer: An Analysis of Common Epidemiological, Genetic, and Biochemical Features Endocr. Rev., August 1, 1998; 19(4): 365 - 396. [Abstract] [Full Text] [PDF]
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H. F. Escobar-Morreale, J. Serrano-Gotarredona, S. Avila, J. Villar-Palasí, C. Varela, and J. Sancho The Increased Circulating Prostate-Specific Antigen Concentrations in Women with Hirsutism Do Not Respond to Acute Changes in Adrenal or Ovarian Function J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2580 - 2584. [Abstract] [Full Text]
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D. N. Melegos and E. P. Diamandis Is Prostate-Specific Antigen Present in Female Serum? Clin. Chem., March 1, 1998; 44(3): 691 - 692. [Full Text] [PDF]
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G. M. Lambert-Messerlian, J. A. Canick, D. N. Melegos, and E. P. Diamandis Increased concentrations of prostate-specific antigen in maternal serum from pregnancies affected by fetal Down syndrome Clin. Chem., February 1, 1998; 44(2): 205 - 208. [Abstract] [Full Text] [PDF]
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N. Zarghami, L. Grass, E. R. Sauter, and E. P. Diamandis Prostate-specific antigen in serum during the menstrual cycle Clin. Chem., October 1, 1997; 43(10): 1862 - 1867. [Abstract] [Full Text] [PDF]
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T. Lovgren, P. Heinonen, P. Lehtinen, H. Hakala, J. Heinola, R. Harju, H. Takalo, V.-M. Mukkala, R. Schmid, H. Lonnberg, et al. Sensitive bioaffinity assays with individual microparticles and time-resolved fluorometry Clin. Chem., October 1, 1997; 43(10): 1937 - 1943. [Abstract] [Full Text] [PDF]
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E. P. Diamandis, S. Nadkarni, B. Bhaumik, A. Abdelrahman, D. N. Melegos, G. Borchert, M. H. Black, M. Alonso, A. Salas, J. R. de los Toyos, et al. Immunofluorometric assay of pepsinogen C and preliminary clinical applications Clin. Chem., August 1, 1997; 43(8): 1365 - 1371. [Abstract] [Full Text] [PDF]
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S.-F. Chen, Y. Xu, and M. P.-C. Ip Electrochemical Enzyme Immunoassay for Serum Prostate-Specific Antigen at Low Concentrations Clin. Chem., August 1, 1997; 43(8): 1459 - 1461. [Full Text]
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F. T. Kreutz and M. R. Suresh Novel bispecific immunoprobe for rapid and sensitive detection of prostate-specific antigen Clin. Chem., April 1, 1997; 43(4): 649 - 656. [Abstract] [Full Text] [PDF]
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D. N. Melegos, H. Yu, M. Ashok, C. Wang, F. Stanczyk, and E. P. Diamandis Prostate-Specific Antigen in Female Serum, a Potential New Marker of Androgen Excess J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 777 - 780. [Abstract] [Full Text] [PDF]
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