Clinical evaluation of free PSA/Total PSA (Prostate-specific Antigen) ratio in the diagnosis of prostate cancer

1997 ◽  
Vol 33 (8) ◽  
pp. 1226-1229 ◽  
Author(s):  
X Filella ◽  
J Alcover ◽  
R Molina ◽  
A Rodríguez ◽  
P Carretero ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Clinical Evaluation ◽  
Specific Antigen ◽  
Free Psa ◽  
Total Psa

scholarly journals The Combination of Human Glandular Kallikrein and Free Prostate-specific Antigen (PSA) Enhances Discrimination Between Prostate Cancer and Benign Prostatic Hyperplasia in Patients with Moderately Increased Total PSA

1999 ◽  
Vol 45 (11) ◽  
pp. 1960-1966 ◽  
Author(s):  
Angeliki Magklara ◽  
Andreas Scorilas ◽  
William J Catalona ◽  
Eleftherios P Diamandis
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Prostate Specific Antigen ◽  
Prostatic Carcinoma ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Prostatic Hyperplasia ◽  
Free Psa ◽  
Glandular Kallikrein ◽  
Total Psa

Abstract Background: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4–10 μg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic “gray zone”. Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. Methods: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5–10 μg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. Results: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5–10 μg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 μg/L who had cancer. Conclusions: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 μg/L who have high probability of cancer and who should be considered for biopsy.

scholarly journals Novel immunoassay for the measurement of complexed prostate-specific antigen in serum

1998 ◽  
Vol 44 (6) ◽  
pp. 1216-1223 ◽  
Author(s):  
W Jeffrey Allard ◽  
Zeqi Zhou ◽  
Kwok K Yeung
Keyword(s):  
Prostate Cancer ◽  
Monoclonal Antibody ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Binding Properties ◽  
Prostate Disease ◽  
Free Psa ◽  
Total Psa ◽  
Benign Prostate ◽  
Artificial Mixtures

Abstract Serum prostate-specific antigen (PSA) is an effective diagnostic tool for detection of prostate cancer (CaP) at an early and potentially curable stage, but specificity is low. Studies have shown that the proportion of serum PSA complexed with α-1-antichymotrypsin (ACT) is higher in men with CaP than in men with benign prostate disease. We developed a novel immunoassay for complexed PSA based on the unique binding properties of a monoclonal antibody that fails to bind free PSA in the presence of antibodies specific for free PSA. The assay measured mixtures of free and complexed PSA accurately, and the measured values of free + complexed PSA in artificial mixtures and in patient sera were equivalent to the measured value of total PSA. Both the serum concentration and the proportion of complexed PSA was substantially higher in patients with CaP compared with patients with benign prostate disease. The cPSA assay may have utility in improving specificity in screening for prostate cancer.

Prostate-Specific Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection

2010 ◽  
Vol 57 (6) ◽  
pp. 921-927 ◽  
Author(s):  
Flip H. Jansen ◽  
Ron H.N. van Schaik ◽  
Joep Kurstjens ◽  
Wolfgang Horninger ◽  
Helmut Klocker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diagnostic Accuracy ◽  
Prostate Specific Antigen ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Prostate Cancer Detection ◽  
Free Psa ◽  
Total Psa

scholarly journals 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 ◽  
Vol 47 (8) ◽  
pp. 1415-1423 ◽  
Author(s):  
Pauliina Nurmikko ◽  
Kim Pettersson ◽  
Timo Piironen ◽  
Jonas Hugosson ◽  
Hans Lilja
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Screening Program ◽  
Specific Antigen ◽  
Benign Disease ◽  
Free Psa ◽  
Plasma Measurement ◽  
Edta Plasma ◽  
Capture Antibody ◽  
Total Psa

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 μg/L). Results: The detection limit of the fPSA-I assay was 0.035 μg/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.

scholarly journals Measurement of the Complex between Prostate-specific Antigen and α1-Protease Inhibitor in Serum

1999 ◽  
Vol 45 (6) ◽  
pp. 814-821 ◽  
Author(s):  
Wan-Ming Zhang ◽  
Patrik Finne ◽  
Jari Leinonen ◽  
Satu Vesalainen ◽  
Stig Nordling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protease Inhibitor ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Serum Samples ◽  
Free Psa ◽  
Total Psa ◽  
Healthy Females

Abstract Background: Prostate-specific antigen (PSA) occurs in serum both free and in complex with protease inhibitors. The complex with α1-antichymotrypsin (ACT) is the major form in serum, and the proportion of PSA-ACT is higher in prostate cancer (PCa) than in benign prostatic hyperplasia (BPH). PSA also forms a complex with α1-protease inhibitor (API) in vitro, and the PSA-ACT complex has been detected in serum from patients with prostate cancer. The aim of the present study was to develop a quantitative method for the determination of PSA-API and to determine the serum concentrations in patients with PCa and BPH. Methods: The assay for PSA-API utilizes a monoclonal antibody to PSA as capture and a polyclonal antibody to API labeled with a Eu-chelate as a tracer. For calibrators, PSA-API formed in vitro was used. Serum samples were obtained before treatment from 82 patients with PCa, from 66 patients with BPH, and from 22 healthy females. Results: The concentrations of PSA-API are proportional to the concentrations of total PSA. PSA-API comprises 1.0–7.9% (median, 2.4%) of total immunoreactive PSA in PCa and 1.3–12.2% (median, 3.6%) in BPH patients with serum PSA concentrations >4 μg/L. In patients with 4–20 μg/L total PSA, the proportion of PSA-API serum is significantly higher in BPH (median, 4.1%) than in PCa (median, 3.2%; P = 0.02). Conclusions: The proportion of PSA-API in serum is lower in patients with PCa than in those with BPH. These results suggest that PSA-API is a potential adjunct to total and free PSA in the diagnosis of prostate cancer.

scholarly journals Between-Method Differences in Prostate-Specific Antigen Assays Affect Prostate Cancer Risk Prediction by Nomograms

2011 ◽  
Vol 57 (7) ◽  
pp. 995-1004 ◽  
Author(s):  
Carsten Stephan ◽  
Kerstin Siemßen ◽  
Henning Cammann ◽  
Frank Friedersdorff ◽  
Serdar Deger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Risk Prediction ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Roc Curves ◽  
Median Percentage ◽  
Free Psa ◽  
Different Types ◽  
Total Psa

BACKGROUND To date, no published nomogram for prostate cancer (PCa) risk prediction has considered the between-method differences associated with estimating concentrations of prostate-specific antigen (PSA). METHODS Total PSA (tPSA) and free PSA were measured in 780 biopsy-referred men with 5 different assays. These data, together with other clinical parameters, were applied to 5 published nomograms that are used for PCa detection. Discrimination and calibration criteria were used to characterize the accuracy of the nomogram models under these conditions. RESULTS PCa was found in 455 men (58.3%), and 325 men had no evidence of malignancy. Median tPSA concentrations ranged from 5.5 μg/L to 7.04 μg/L, whereas the median percentage of free PSA ranged from 10.6% to 16.4%. Both the calibration and discrimination of the nomograms varied significantly across different types of PSA assays. Median PCa probabilities, which indicate PCa risk, ranged from 0.59 to 0.76 when different PSA assays were used within the same nomogram. On the other hand, various nomograms produced different PCa probabilities when the same PSA assay was used. Although the ROC curves had comparable areas under the ROC curve, considerable differences were observed among the 5 assays when the sensitivities and specificities at various PCa probability cutoffs were analyzed. CONCLUSIONS The accuracy of the PCa probabilities predicted according to different nomograms is limited by the lack of agreement between the different PSA assays. This difference between methods may lead to unacceptable variation in PCa risk prediction. A more cautious application of nomograms is recommended.

scholarly journals Anti-Free Prostate-specific Antigen Monoclonal Antibody Epitopes Defined by Mimotopes and Molecular Modeling

1999 ◽  
Vol 45 (5) ◽  
pp. 638-650 ◽  
Author(s):  
Sandrine Michel ◽  
Gilbert Deléage ◽  
Jean-Philippe Charrier ◽  
Jacques Passagot ◽  
Nicole Battail-Poirot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Modeling ◽  
Enzymatic Activity ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Free Psa ◽  
Total Psa ◽  
Sandwich Assays ◽  
Antibody Epitopes

Abstract Background: Prostate-specific antigen (PSA) is an important marker for the diagnosis and management of prostate cancer, and the free PSA/total PSA ratio has been shown to be efficient for distinguishing prostate cancer from benign prostatic hyperplasia. We report here the characterization of seven mouse monoclonal antibodies (mAbs) and the partial localization of two conformational epitopes identified by anti-free PSA mAbs. Methods: The mAbs were studied by competition and sandwich assays, and the epitope localization of the two anti-free PSA mAbs (6C8D8 and 5D3D11) was performed using phage displayed peptide libraries and molecular modeling. Results: The seven mAbs were classified into three groups according to their recognition specificities and their ability to inhibit the enzymatic activity of PSA and the formation of PSA-α1-antichymotrypsin (ACT) complex. Among the anti-free PSA mAb group, 6C8D8 recognized the phage displayed peptide RKLRPHWLHFHPVAV, two parts of which presented similarities with two regions distant on the PSA sequence but joined in the tridimensional structure. mAb 5D3D11 recognized the peptide DTPYPWGWLLDEGYD, which is similar to a PSA region located on the board of the groove containing the PSA enzymatic site. Both epitopes were located in the theoretical ACT binding site described previously. Moreover, these mAbs were able to inhibit the enzymatic activity of PSA. Conclusions: These epitope localizations are in agreement with the ability of both mAbs to inhibit enzymatic activity and ACT fixation. The results presented here could bring information for the generation of clinically relevant PSA assays.

scholarly journals Percent free prostate-specific antigen in assessing the probability of prostate cancer under optimal analytical conditions

1998 ◽  
Vol 44 (12) ◽  
pp. 2462-2470 ◽  
Author(s):  
Massimo Gion ◽  
Riccardo Mione ◽  
Paola Barioli ◽  
Mario Barichello ◽  
Filiberto Zattoni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Diagnostic Performance ◽  
False Negative ◽  
Specific Antigen ◽  
Free Psa ◽  
Post Test ◽  
Total Psa ◽  
Post Test Probability ◽  
Test Probability

Abstract Although general consensus exists that percent free prostate-specific antigen (PSA) is superior to total immunoreactive PSA for prostate cancer (CaP) detection, its diagnostic performance is not yet well established. Analytical problems may account for difficulties in evaluating percent free PSA because the free PSA concentration is substantially lower than that of total PSA. The aim of the present study was to establish the diagnostic performances of the IMMULITE percent free PSA assay from Diagnostics Products Corp. under experimental conditions optimized to minimize analytical variability. Eighty-five patients with untreated primary CaP and 261 with untreated benign prostate hypertrophy (BPH) were prospectively enrolled. The Diagnostics Products IMMULITE total (Third Generation) and free PSA were measured by the same technician, using the same instrument and the same reagent batch. We calculated the post-test probability to express how the likelihood of the diagnosis of CaP changed after the percent free PSA was determined. Areas under the ROC curves of percent free PSA were better than those of total PSA in every evaluated range of total PSA. The percent free PSA could have reduced the rate of unnecessary biopsies by 47% in patients with total PSA ≥4 μg/L with only 3.8% false-negative results. The post-test probability of percent free PSA was, however, <50% in men 50–70 years of age, using cutoff points providing sensitivity from 99% to 80%. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 μg/L. In men with low total PSA, the diagnostic performance of the percent free PSA assay may be optimized by controlling methodological variability. The percent free PSA assay is effective in reducing the rate of unnecessary biopsies in men with total PSA >4 μg/L. However, the post-test probability provided by percent free PSA is relatively low in asymptomatic patients 50–70 years of age.

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