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Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum

Phronen, T ; Haese, A ; Huland, H ; Steuber, T ; Christensen, IJ ; Brunner, N ; Dano, K ; Hoyer-Hansen, G and Lilja, Hans LU (2006) In Clinical Chemistry 52(5). p.838-844
Abstract
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... (More)
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 mu g/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 mu g/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. (c) 2006 American Association for Clinical Chemistry. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Chemistry
volume
52
issue
5
pages
838 - 844
publisher
American Association for Clinical Chemistry
external identifiers
  • pmid:16543389
  • wos:000237339600009
  • scopus:33646336629
ISSN
0009-9147
DOI
10.1373/clinchem.2005.064253
language
English
LU publication?
yes
id
be4193f8-fbb5-43a6-8d29-a2a0c1ed5f69 (old id 410151)
date added to LUP
2016-04-01 11:59:54
date last changed
2020-01-12 09:00:55
@article{be4193f8-fbb5-43a6-8d29-a2a0c1ed5f69,
  abstract     = {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 mu g/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 mu g/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. (c) 2006 American Association for Clinical Chemistry.},
  author       = {Phronen, T and Haese, A and Huland, H and Steuber, T and Christensen, IJ and Brunner, N and Dano, K and Hoyer-Hansen, G and Lilja, Hans},
  issn         = {0009-9147},
  language     = {eng},
  number       = {5},
  pages        = {838--844},
  publisher    = {American Association for Clinical Chemistry},
  series       = {Clinical Chemistry},
  title        = {Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum},
  url          = {http://dx.doi.org/10.1373/clinchem.2005.064253},
  doi          = {10.1373/clinchem.2005.064253},
  volume       = {52},
  year         = {2006},
}