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.

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 Proenzyme Forms of Prostate-Specific Antigen in Serum Improve the Detection of Prostate Cancer

2004 ◽  
Vol 50 (6) ◽  
pp. 1017-1025 ◽  
Author(s):  
Stephen D Mikolajczyk ◽  
William J Catalona ◽  
Cindy L Evans ◽  
Harry J Linton ◽  
Lisa S Millar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Cancer Detection ◽  
Specific Antigen ◽  
Serum Markers ◽  
Prostate Cancer Detection ◽  
Good Marker ◽  
Free Psa ◽  
Specificity And Sensitivity ◽  
Benign Prostate

Abstract Introduction: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively]. Methods: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4–10 μg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. Results: The proPSA forms had quantification limits of 0.015–0.025 μg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64–0.74), 0.64 (0.58–0.68), 0.63 (0.58–0.68), and 0.57 (0.51–0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66–0.86), with 90% sensitivity and 36% specificity at 0.04 μg/L. Conclusions: The percentage of proPSA gave better cancer detection in the 4–10 μg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.

scholarly journals PREPARASI PEREAKSI KIT IMMUNORADIOMETRlCASSAY FREE PROSTATE SPECIFIC ANTIGEN UNTUK DETEKSI KANKER PROSTAT

2013 ◽  
Vol 15 (2) ◽  
pp. 14-24
Author(s):  
Puji Widayati ◽  
Gina Mondrida ◽  
Sri Setiyowati ◽  
Agus Ariyanto ◽  
V. Yulianti Susilo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Prostatic Hyperplasia ◽  
Free Condition ◽  
Free Psa ◽  
Prostate Enlargement ◽  
Assay Design ◽  
Benign Prostate

Prostate Specific Antigen (PSA) is a glycoprotein with a molecular weight of approximately 34,000 daltons serine protease secreted exclusively by prostatic epithelial cells that lining acini and prostate gland. Increased of PSA levels can be caused by prostate cancer or benign prostate enlargement (benign prostatic hyperplasia, BPH). PSA in the blood was found in the free condition (free PSA) and most of the bound protein (complexed-PSA, c-PSA). Measuring levels of PSA was found in the blood can be done by several methods such as by immunoradiometricassay (IRMA) methods or ELISA methods. IRMA method is one of immunoassay techniques using radionuclides ,/' 125 oJ I as a tracer, so the sample in small 13 quantity can be detected The purpose of this study was obtained PSA reagent kit that includes 1251labeled PSA as a tracer, PSA coated tube and PSA standard that requirements of the kit, then it can be optimized assay design, that eventually PSA reagent kit can be used for early detection of prostate cancer. It has been done labeling of Mab PSA using 125 1with reaction time was 90 seconds, amount of PSA MAb was 75 ugram and the activity of Na_ 125I was 1000 flCi. Preaparation of PSA coated tube using 0.05 M Na2C03 solution, at pH: 9.6 with volume was 250 ml., standard PSA with 0.025 Mphosphate buffer at pH 7.4 containing 5% BSA and 0.1% NaN3, and resulting at 1,25% and 14,12% respectively of NSB and BIT that requirement of the kit.Keywords: Prostate cancer, PSA, IRMA,NSB, Maximum Binding

scholarly journals Comparison of prostate-specific antigen (PSA) measured by four combinations of free PSA and total PSA assays

1997 ◽  
Vol 43 (9) ◽  
pp. 1588-1594 ◽  
Author(s):  
Ralf Junker ◽  
Burkhard Brandt ◽  
Christian Zechel ◽  
Gerd Assmann
Keyword(s):  
Prostate Specific Antigen ◽  
Patient Population ◽  
Specific Antigen ◽  
Prostate Hyperplasia ◽  
Predictive Values ◽  
Negative Results ◽  
Free Psa ◽  
Gray Area ◽  
Total Psa ◽  
Benign Prostate

Abstract We compared prostate-specific antigen (PSA) assay systems [i.e., free PSA (f-PSA) and the corresponding total PSA (t-PSA) assay] from four different manufacturers as well as the f-PSA/t-PSA ratios with regard to their ability to discriminate between benign prostate hyperplasia (BPH) and prostate cancer (PCA). ROC analysis showed similar areas under the curves (AUCs) with different assay systems. For the entire patient population the AUCs of the f-PSA/t-PSA ratio were not or slightly increased compared with the sole measurement of t-PSA (t-PSA, 0.792–0.820; f-PSA/t-PSA ratio, 0.685–0.859). In contrast, for only those patients who showed t-PSA concentrations within the diagnostic gray area of 4–25 μg/L t-PSA, the AUCs were greater for the f-PSA/t-PSA ratio than for measurement of t-PSA alone (t-PSA, 0.608–0.647; f-PSA/t-PSA ratio, 0.690–0.806). These results were confirmed by the predictive values of the negative results (NPVs) of the t-PSA assays and the f-PSA/t-PSA ratios (assay thresholds corresponding to a 95% detection limit). Compared with the sole t-PSA measurement there was no mentionable increase in the NPVs due to the f-PSA/t-PSA ratio for the entire patient population, but an increase up to 49% when limited to t-PSA concentrations within 4–25 μg/L. We therefore conclude that the f-PSA/t-PSA ratio may be helpful for differential diagnosis of BPH and PCA within the diagnostic gray area of 4–25 μg/L t-PSA.

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

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 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.

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