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Discrimination of prostate cancer from benign disease by selective measurements of serum subfractions of free PSA that are not internally cleaved at Lys145-Lys146

Nurmikko, Pauliina ; Steuber, Thomas ; Haese, Alexander ; Pettersson, Kim ; Hammerer, Peter ; Huland, Hartwig and Lilja, Hans LU orcid (2002) In Journal of Clinical Ligand Assay 25(1). p.67-69
Abstract

Background: The free PSA fraction in serum of patients with various prostatic disorders is essentially unreactive with the anti-proteases in blood. Recently reported data show that it is likely to consist of a mixture of proPSA, internally cleaved PSA forms, and possibly other uncharacterized forms. Currently there are no specific methods available to measure the different free PSA subfractions and to evaluate their diagnostic or prognostic value. Methods: A novel immunoassay has been developed that measures intact, free PSA, which is not internally cleaved at Lys145-Lys146. Sera with total PSA-levels (PSA-T) from 2 to 8 ng/mL were obtained from 112 men without prostate cancer (with negative sextant biopsy or benign prostatic... (More)

Background: The free PSA fraction in serum of patients with various prostatic disorders is essentially unreactive with the anti-proteases in blood. Recently reported data show that it is likely to consist of a mixture of proPSA, internally cleaved PSA forms, and possibly other uncharacterized forms. Currently there are no specific methods available to measure the different free PSA subfractions and to evaluate their diagnostic or prognostic value. Methods: A novel immunoassay has been developed that measures intact, free PSA, which is not internally cleaved at Lys145-Lys146. Sera with total PSA-levels (PSA-T) from 2 to 8 ng/mL were obtained from 112 men without prostate cancer (with negative sextant biopsy or benign prostatic hyperplasia [BPH]) and 125 men with biopsy-proven clinically localized prostate cancer (PCa) before treatment. The aim was to determine levels of intact free PSA (fPSA-I) in serum of these patients and to determine the diagnostic value of fPSA-I. Results: The ratio of intact fPSA to free PSA (PSA-F) is significantly higher in serum from men with prostate cancer (median 47.6%) compared to those without cancer (median 41.3%; P = 0.0057). Logistic regression analysis was used to calculate the predictive values for fPSA-I + PSA-F + PSA-T (Log II, F, TI). Analysis showed that each of the three analytes contributed significantly to the discrimination of PCa from non-cancer sera. The area under the curve (AUC) of Log [I, F, T] was significantly larger (AUC = 0.7041) compared to the AUC of PSA-T (AUC = 0.5960; P = 0.0038) whereas the AUC of F/T ratio (AUC = 0.6669) was not (P= 0.16). Conclusion: The ratio of intact to free PSA was significantly higher in prostate cancer compared to the noncancer or benign group. Combination of fPSA-I, PSA-F and PSA-T improved discrimination of prostate cancer from non-cancer sera, especially at low PSA-T concentrations.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Free PSA, Immunoassay, Internal cleavage, Prostate cancer
in
Journal of Clinical Ligand Assay
volume
25
issue
1
pages
67 - 69
publisher
Clinical Ligand Assay Society Inc.
external identifiers
  • scopus:0036513711
ISSN
1081-1672
language
English
LU publication?
no
id
84e45a37-db51-4911-a1c0-412c0b180244
date added to LUP
2022-12-17 17:08:54
date last changed
2022-12-20 02:30:08
@article{84e45a37-db51-4911-a1c0-412c0b180244,
  abstract     = {{<p>Background: The free PSA fraction in serum of patients with various prostatic disorders is essentially unreactive with the anti-proteases in blood. Recently reported data show that it is likely to consist of a mixture of proPSA, internally cleaved PSA forms, and possibly other uncharacterized forms. Currently there are no specific methods available to measure the different free PSA subfractions and to evaluate their diagnostic or prognostic value. Methods: A novel immunoassay has been developed that measures intact, free PSA, which is not internally cleaved at Lys145-Lys146. Sera with total PSA-levels (PSA-T) from 2 to 8 ng/mL were obtained from 112 men without prostate cancer (with negative sextant biopsy or benign prostatic hyperplasia [BPH]) and 125 men with biopsy-proven clinically localized prostate cancer (PCa) before treatment. The aim was to determine levels of intact free PSA (fPSA-I) in serum of these patients and to determine the diagnostic value of fPSA-I. Results: The ratio of intact fPSA to free PSA (PSA-F) is significantly higher in serum from men with prostate cancer (median 47.6%) compared to those without cancer (median 41.3%; P = 0.0057). Logistic regression analysis was used to calculate the predictive values for fPSA-I + PSA-F + PSA-T (Log II, F, TI). Analysis showed that each of the three analytes contributed significantly to the discrimination of PCa from non-cancer sera. The area under the curve (AUC) of Log [I, F, T] was significantly larger (AUC = 0.7041) compared to the AUC of PSA-T (AUC = 0.5960; P = 0.0038) whereas the AUC of F/T ratio (AUC = 0.6669) was not (P= 0.16). Conclusion: The ratio of intact to free PSA was significantly higher in prostate cancer compared to the noncancer or benign group. Combination of fPSA-I, PSA-F and PSA-T improved discrimination of prostate cancer from non-cancer sera, especially at low PSA-T concentrations.</p>}},
  author       = {{Nurmikko, Pauliina and Steuber, Thomas and Haese, Alexander and Pettersson, Kim and Hammerer, Peter and Huland, Hartwig and Lilja, Hans}},
  issn         = {{1081-1672}},
  keywords     = {{Free PSA; Immunoassay; Internal cleavage; Prostate cancer}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{67--69}},
  publisher    = {{Clinical Ligand Assay Society Inc.}},
  series       = {{Journal of Clinical Ligand Assay}},
  title        = {{Discrimination of prostate cancer from benign disease by selective measurements of serum subfractions of free PSA that are not internally cleaved at Lys145-Lys146}},
  volume       = {{25}},
  year         = {{2002}},
}