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Discrimination of benign from malignant prostatic disease by selective measurements of single chain, intact free prostate specific antigen

Steuber, T; Nurmikko, P; Haese, A; Pettersson, K; Graefen, M; Hammerer, P; Huland, H and Lilja, Hans LU (2002) In Journal of Urology 168(5). p.1917-1922
Abstract
Purpose: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. Materials and Methods: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting... (More)
Purpose: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. Materials and Methods: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng/ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis. Results: The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p <0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p <0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng/ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704, p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602). Conclusions: By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
prostatic neoplasms, prostate-specific antigen, diagnosis
in
Journal of Urology
volume
168
issue
5
pages
1917 - 1922
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000178562100004
  • pmid:12394676
  • scopus:0036837259
ISSN
1527-3792
DOI
10.1016/S0022-5347(05)64263-2
language
English
LU publication?
yes
id
1618269a-d78e-41f1-9f7c-a7541d81302a (old id 325553)
date added to LUP
2007-11-09 12:30:47
date last changed
2017-01-01 07:27:14
@article{1618269a-d78e-41f1-9f7c-a7541d81302a,
  abstract     = {Purpose: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. Materials and Methods: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng/ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis. Results: The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p &lt;0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p &lt;0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng/ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704, p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602). Conclusions: By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation.},
  author       = {Steuber, T and Nurmikko, P and Haese, A and Pettersson, K and Graefen, M and Hammerer, P and Huland, H and Lilja, Hans},
  issn         = {1527-3792},
  keyword      = {prostatic neoplasms,prostate-specific antigen,diagnosis},
  language     = {eng},
  number       = {5},
  pages        = {1917--1922},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Discrimination of benign from malignant prostatic disease by selective measurements of single chain, intact free prostate specific antigen},
  url          = {http://dx.doi.org/10.1016/S0022-5347(05)64263-2},
  volume       = {168},
  year         = {2002},
}