HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: clinchem.2005.064253v1 52/5/838    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Piironen, T. Articles by Lilja, H. Search for Related Content PubMed PubMed Citation Articles by Piironen, T. Articles by Lilja, H. Related Collections Proteomics and Protein Markers Cancer Diagnostics (since 2002)

Enhanced Discrimination of Benign from Malignant Prostatic Disease by Selective Measurements of Cleaved Forms of Urokinase Receptor in Serum

¹ The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
² Department of Urology, University Clinic Hamburg Eppendorf, Hamburg, Germany.
³ Institute of Pathobiology, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
⁴ Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, University Hospital (UMAS), Malmö, Sweden.
⁵ Departments of Clinical Laboratories, Urology, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
⁶ Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark.

^aAddress correspondence to this author at: Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 213, New York, NY 10021. Fax 646-422-2379; e-mail LiljaH{at}mskcc.org.

Background: Early detection of prostate cancer (PCa) centers on measurements of prostate-specific antigen (PSA), but current testing practices suffer from lack of specificity and generate many unnecessary prostate biopsies. Soluble urokinase plasminogen activator receptor (uPAR) is present in blood in both intact and cleaved forms. Increased uPAR in blood is correlated with poor prognosis in various cancers, but uPAR has not been shown to be useful in PCa diagnostics. We assessed the ability of immunoassays for specific uPAR forms to discriminate PCa from benign conditions.

Methods: We measured total PSA (tPSA), free PSA (fPSA), intact uPAR [uPAR(I-III)], intact uPAR + cleaved uPAR domains II+III [uPAR(I-III) + uPAR(II-III)], and cleaved uPAR domain I [uPAR(I)] in sera from 224 men with and 166 men without PCa. We assessed differences in serum concentrations between the PCa and noncancer groups within the entire cohort and in men with tPSA concentrations of 2–10 µg/L. The diagnostic accuracy of individual analytes and analyte combinations was explored by logistic regression and ROC analyses and evaluations of sensitivity and specificity pairs.

Results: Serum uPAR(I) and uPAR(II-III) were higher in PCa than in benign disease. In men with tPSA between 2 and 10 µg/L, the combination of %fPSA with the ratio uPAR(I)/uPAR(I-III) had a greater area under the ROC curve (0.73) than did %fPSA (0.68).

Conclusions: Specific measurements of different uPAR forms in serum improve the specificity of PCa detection. The uPAR forms may therefore be complementary to PSA for PCa detection, most importantly in men with moderately increased PSA.

The following articles in journals at HighWire Press have cited this article:

				H. Lilja, A. Vickers, and P. Scardino Measurements of Proteases or Protease System Components in Blood to Enhance Prediction of Disease Risk or Outcome in Possible Cancer J. Clin. Oncol., February 1, 2007; 25(4): 347 - 348. [Full Text] [PDF]

				T. Steuber, A. J. Vickers, A. M. Serio, V. Vaisanen, A. Haese, K. Pettersson, J. A. Eastham, P. T. Scardino, H. Huland, and H. Lilja Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer Clin. Chem., February 1, 2007; 53(2): 233 - 240. [Abstract] [Full Text] [PDF]