Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146
(2001) In Clinical Chemistry 47(8). p.1415-1423- Abstract
- BACKGROUND: The proportion of free prostate-specific antigen (PSA) is higher in the sera of patients with benign prostatic hyperplasia compared with patients with prostate cancer (PCa). We developed an immunoassay that measures intact, free PSA forms (fPSA-I), but does not detect free PSA that has been internally cleaved at Lys145-Lys146 (fPSA-N), and investigated whether this form could discriminate patients with PCa from those without PCa. METHODS: The assay for fPSA-I uses a novel monoclonal antibody (MAb) that does not detect PSA that has been internally cleaved at Lys145-Lys146. A MAb specific for free PSA was used as a capture antibody, and purified recombinant proPSA was used as a calibrator. The concentrations of fPSA-I, free PSA... (More)
- BACKGROUND: The proportion of free prostate-specific antigen (PSA) is higher in the sera of patients with benign prostatic hyperplasia compared with patients with prostate cancer (PCa). We developed an immunoassay that measures intact, free PSA forms (fPSA-I), but does not detect free PSA that has been internally cleaved at Lys145-Lys146 (fPSA-N), and investigated whether this form could discriminate patients with PCa from those without PCa. METHODS: The assay for fPSA-I uses a novel monoclonal antibody (MAb) that does not detect PSA that has been internally cleaved at Lys145-Lys146. A MAb specific for free PSA was used as a capture antibody, and purified recombinant proPSA was used as a calibrator. The concentrations of fPSA-I, free PSA (PSA-F), and total PSA (PSA-T) were analyzed in EDTA-plasma samples (n = 276) from patients who participated in a screening program for PCa (PSA-T, 0.83-76.3 microg/L). RESULTS: The detection limit of the fPSA-I assay was 0.035 microg/L. Both the measured concentrations of fPSA-I and the concentrations of fPSA-N (calculated as PSA-F - fPSA-I) provided statistically significant discrimination of the two clinical groups. By contrast, PSA-F did not discriminate between these groups. Each of the ratios fPSA-I/PSA-F, fPSA-N/PSA-T, and PSA-F/PSA-T separated cancer samples from noncancer samples in a statistically significant manner (P <0.0001). The ratio fPSA-I/PSA-F was significantly higher in cancer (median, 59%) compared with noncancer samples (47%). CONCLUSIONS: The ratio fPSA-I/PSA-F is significantly higher in cancer compared with noncancer. The percentages of both fPSA-N/PSA-T and fPSA-I/PSA-F may provide interesting diagnostic enhancements alone or in combination with other markers and require further studies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1121902
- author
- Nurmikko, Pauliina ; Pettersson, Kim ; Piironen, Timo ; Hugosson, Jonas and Lilja, Hans LU
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Clinical Chemistry
- volume
- 47
- issue
- 8
- pages
- 1415 - 1423
- publisher
- American Association for Clinical Chemistry
- external identifiers
-
- pmid:11468231
- scopus:0034921328
- ISSN
- 0009-9147
- language
- English
- LU publication?
- yes
- id
- ff77ae07-9961-4bba-a224-d5ab2ae2f97b (old id 1121902)
- alternative location
- http://www.clinchem.org/cgi/reprint/47/8/1415
- date added to LUP
- 2016-04-01 12:01:36
- date last changed
- 2022-04-21 01:19:59
@article{ff77ae07-9961-4bba-a224-d5ab2ae2f97b, abstract = {{BACKGROUND: The proportion of free prostate-specific antigen (PSA) is higher in the sera of patients with benign prostatic hyperplasia compared with patients with prostate cancer (PCa). We developed an immunoassay that measures intact, free PSA forms (fPSA-I), but does not detect free PSA that has been internally cleaved at Lys145-Lys146 (fPSA-N), and investigated whether this form could discriminate patients with PCa from those without PCa. METHODS: The assay for fPSA-I uses a novel monoclonal antibody (MAb) that does not detect PSA that has been internally cleaved at Lys145-Lys146. A MAb specific for free PSA was used as a capture antibody, and purified recombinant proPSA was used as a calibrator. The concentrations of fPSA-I, free PSA (PSA-F), and total PSA (PSA-T) were analyzed in EDTA-plasma samples (n = 276) from patients who participated in a screening program for PCa (PSA-T, 0.83-76.3 microg/L). RESULTS: The detection limit of the fPSA-I assay was 0.035 microg/L. Both the measured concentrations of fPSA-I and the concentrations of fPSA-N (calculated as PSA-F - fPSA-I) provided statistically significant discrimination of the two clinical groups. By contrast, PSA-F did not discriminate between these groups. Each of the ratios fPSA-I/PSA-F, fPSA-N/PSA-T, and PSA-F/PSA-T separated cancer samples from noncancer samples in a statistically significant manner (P <0.0001). The ratio fPSA-I/PSA-F was significantly higher in cancer (median, 59%) compared with noncancer samples (47%). CONCLUSIONS: The ratio fPSA-I/PSA-F is significantly higher in cancer compared with noncancer. The percentages of both fPSA-N/PSA-T and fPSA-I/PSA-F may provide interesting diagnostic enhancements alone or in combination with other markers and require further studies.}}, author = {{Nurmikko, Pauliina and Pettersson, Kim and Piironen, Timo and Hugosson, Jonas and Lilja, Hans}}, issn = {{0009-9147}}, language = {{eng}}, number = {{8}}, pages = {{1415--1423}}, publisher = {{American Association for Clinical Chemistry}}, series = {{Clinical Chemistry}}, title = {{Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146}}, url = {{http://www.clinchem.org/cgi/reprint/47/8/1415}}, volume = {{47}}, year = {{2001}}, }