scholarly journals Performance of the 4Kscore Test in Plasma and Serum and Stability of the Component Analytes in Clinical Samples

2018 ◽  
Vol 3 (2) ◽  
pp. 185-199 ◽  
Author(s):  
Christina E Higgins ◽  
Patricia Neybold ◽  
Marcella B Holdridge ◽  
Catherine R Barnes ◽  
Yan Dong ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Specific Antigen ◽  
Clinical Information ◽  
Target Population ◽  
Clinical Samples ◽  
Free Psa ◽  
Total Prostate Specific Antigen ◽  
Edta Plasma ◽  
The Stability ◽  
Intact Psa

Abstract Background The 4Kscore Test determines a personalized risk score for aggressive prostate cancer by combining the blood sample measurements of total prostate-specific antigen (tPSA), free PSA (fPSA), intact PSA (iPSA), and human kallikrein-related peptidase 2 (hK2) with patient clinical information to generate the patient risk's score; thus, accuracy and precision of the 4Kscore depend on the reliability of these measurements. Although tPSA and fPSA are measured on a Food and Drug Administration (FDA)-approved platform, the performance of the iPSA and hK2 assays in the clinical setting has not previously been reported. Methods Analytical performance was determined for the iPSA and hK2 assays in both serum and EDTA plasma, according to Clinical and Laboratory Standards Institute guidelines. Equivalence of the 4Kscore in both sample matrices was demonstrated in a 353-patient clinical cohort, and the stability of endogenous iPSA and hK2 for at least 3 days was demonstrated in a smaller subset. Results Intralaboratory and interlaboratory precision of the iPSA and hK2 assays in both matrices was comparable with that of FDA-approved tPSA and fPSA assays (<18% for iPSA; <8% for hK2). The picogram per milliliter sensitivity and wide dynamic range of the iPSA and hK2 assays allowed for accurate measurements in the target population. The 4Kscore generated in either matrix up to 3 days after collection is equivalent to that measured within 24 h of collection (Passing–Bablok slope 95% CI: plasma, 0.999–1.034; serum, 0.997–1.040). Conclusions The robust performance of component assays and reliable stability of the endogenous analytes in clinical samples proven here ensures an accurate 4Kscore Test result.

Five-Year Stability Study of Free and Total Prostate-Specific Antigen Concentrations in Serum Specimens Collected and Stored at – 70°C or Less

2007 ◽  
Vol 22 (3) ◽  
pp. 206-213 ◽  
Author(s):  
D.A. Scaramuzzino ◽  
K. Schulte ◽  
B.N. Mack ◽  
T.F. Soriano ◽  
H.A. Fritsche
Keyword(s):  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Stability Study ◽  
Regression Analyses ◽  
Altman Analysis ◽  
Time Period ◽  
Total Prostate Specific Antigen ◽  
Deming Regression ◽  
Lower Temperature ◽  
The Stability

The stability of total (t) and free (f) prostate-specific antigen (PSA) in male serum specimens stored at –70°C or lower temperature for 4.7 to 4.9 years was studied. Until now, the stability of these analytes in serum has not been evaluated systematically beyond 2 years of storage at –70°C. Aliquots of frozen serum were thawed in 2001 and 2006 and assayed for tPSA and fPSA using a Dade Behring Dimension(r) RxL analyzer and reagents. tPSA values ranged from 0.07 to 69.94 and 0.00 to 69.83 ng/mL in 2001 and 2006, respectively, whereas fPSA values for the tested specimens ranged from 0.02 to 5.72 and 0.00 to 5.92, respectively. Deming regression analyses showed agreement in assay values over time as tPSA values yielded a slope of 1.0112 and a y-intercept of 0.0195; fPSA values produced a slope 1.0538 and a y-intercept of –0.0442; f/tPSA values yielded a slope of 0.9631 and a y-intercept of 0.1195. A Bland-Altman analysis of the data demonstrated analyte and ratio stability over this time period. We conclude that serum, when collected properly and stored at –70°C or lower temperature, may be used for tPSA and fPSA clinical studies for at least 5 years after collection.

scholarly journals Benign Prostate-specific Antigen (BPSA) in Serum Is Increased in Benign Prostate Disease

2003 ◽  
Vol 49 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Harry J Linton ◽  
Leonard S Marks ◽  
Lisa S Millar ◽  
Christine L Knott ◽  
Harry G Rittenhouse ◽  
...  
Keyword(s):  
Prostate Specific Antigen ◽  
Limit Of Detection ◽  
Specific Antigen ◽  
Clinical Information ◽  
High Specificity ◽  
Wide Distribution ◽  
Cross Reactivity ◽  
Free Psa ◽  
Control Serum ◽  
Benign Prostate

Abstract Background: BPSA is a “benign” form of free prostate-specific antigen (PSA) that is increased in prostate transition zone tissues of men with pathologic benign prostatic hyperplasia (BPH). We developed an immunoassay to determine the concentration of BPSA in the serum of men with BPH. Methods: The BPSA antigen was purified by HPLC, and murine monoclonal antibodies were prepared by standard methods. A fluorogenic ELISA was developed with high specificity for BPSA and no cross-reactivity with other forms of PSA. Results: The BPSA immunoassay had a lower limit of detection of 6 ng/L and a cross-reactivity of <1% with all other clipped and nonclipped forms of PSA. The BPSA antibody was specific for the internal Lys182 cleavage site that characterizes BPSA. Biopsy-negative men with a median total PSA of 4.8 μg/L had a median of 0.22 μg/L BPSA, representing 25% of the free PSA in serum. BPSA ranged from 0% to 60% of the free PSA in serum. BPSA in a cohort of cancer serum also comprised 25% of the free PSA. Control serum from women or men without increased PSA had nondetectable BPSA. Conclusions: BPSA is a significant percentage of the free PSA in BPH serum but not in control serum. The presence of prostate cancer does not alter the relative proportions of BPSA in sera with <10 μg/L PSA. BPSA has a wide distribution of concentrations in the serum and may provide clinical information for the study of men with BPH.

Evaluation of prostate cancer risk in men with PSA < 1.5.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 64-64
Author(s):  
Whitney N. Stanton ◽  
E. David Crawford ◽  
Paul Arangua ◽  
John Hoenemeyer ◽  
Francisco G. La Rosa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Clinical Information ◽  
Mrna Levels ◽  
Protein Biomarkers ◽  
Cancer Awareness ◽  
Free Psa ◽  
Increased Risk ◽  
Total Psa

64 Background: Prostate Specific Antigen (PSA) screening remains controversial primarily because of over detection and treatment. There is an unmet clinical need to identify patients at increased risk for high-grade (HG – Gleason Score ≥7) prostate cancer (PCa) since PSA has low sensitivity. Combining PSA with well-validated prostate cancer biomarkers (PCM) can improve risk assessment. We investigated the performance of three PCMs (phi – prostate health index, 4KScore, and SelectMDx) on patients with PSA levels < 1.5 ng/mL that represent a “safe zone” where risk of any PCa is rare Methods: 652 men were screened for PCa during the annual Prostate Cancer Awareness Week at the University of Colorado Hospital. This study was supported by Prostate Condition Education Council and the Schramm Foundation. phi is evaluated using p2PSA, total PSA, and free PSA in serum. Phi < 52.7 suggests absence of HG PCa. 4KScore incorporates four kallikrein protein biomarkers: total PSA, free PSA, intact PSA, human kallikrein protein, and clinical information. A 4KScore < 20% suggests absence of HG PCa. The SelectMDx post-DRE urine test measures mRNA levels of the homeobox C6 and distal-less homeobox 1 biomarkers. SelectMDx score of 0% indicates absence of HG PCa. Results: No patients with a PSA < 1.5 had SelectMDx > 0% and/or phi > 52.7. One patient had a 4KScore of 27%, indicating a risk for HG PCa. For patients with PSA between 1.5-3.99, 2.9% (4/135), 7.4% (4/54), and 2.3% (2/85) had positive phi, 4KScore, and SelectMDx results, respectively. Conclusions: Men with PSA <1.5 ng/mL are at very low risk for HG PCa. Men with PSA between 1.5-3.99 with positive PCM results may be referred for further evaluation. [Table: see text]

scholarly journals Effect of the Ratio of Free to Total Prostate-specific Antigen on Interassay Variability in Proficiency Test Samples

1999 ◽  
Vol 45 (8) ◽  
pp. 1181-1189 ◽  
Author(s):  
M Pat Fox ◽  
Andrew A Reilly ◽  
Erasmus Schneider
Keyword(s):  
Prostate Specific Antigen ◽  
Proficiency Test ◽  
Seminal Fluid ◽  
Specific Antigen ◽  
Free Form ◽  
Sample Mean ◽  
Substantial Impact ◽  
Free Psa ◽  
Total Prostate Specific Antigen ◽  
Total Psa

Abstract Background: Up to sevenfold differences were observed between total prostate-specific antigen (PSA) methods for New York State Proficiency Test samples prepared with seminal fluid PSA in human female serum. Because the PSA was mainly in its free form under these conditions, we wanted to determine whether a defined mixture of free and complexed PSA would reduce the interassay differences. Methods: We prepared a series of five solutions of 60 g/L bovine serum albumin with 10 μg/L total PSA consisting of varied proportions of free, noncomplexible PSA, and α1-antichymotrypsin (ACT)-complexed PSA from 0% to 100%. Two hundred seventy laboratories measured the total PSA in these samples, and 16 laboratories also analyzed the samples for free PSA. The results were used to calculate free/total PSA ratios. Results: Interassay CVs for total PSA measurements were ∼7% at 10–15% free PSA but became gradually larger as the free/total PSA ratio increased. Measured free-PSA concentrations were similar within each sample (mean CV, 12%), and the results were relatively independent of the proportion of free PSA in the samples. Twofold discrepancies between actual and expected ratios were observed with some methods at 100% free PSA and to a lesser degree at 30% free PSA. At 100% free PSA, the relatively higher total-PSA values measured by nonequimolar methods yielded low free/total PSA ratios of 50–60%. In contrast, the lower total PSA values obtained by equimolar methods yielded ratios close to the expected 100%. Conclusions: Preparing proficiency test samples with a 10:90 mixture of free, noncomplexible PSA:PSA-ACT is a viable alternative to the use of seminal fluid PSA. Furthermore, the method used to measure total PSA may have a substantial impact on the calculated proportion of free PSA and hence may have clinical relevance.

Preanalytical stability of [-2]proPSA in whole blood stored at room temperature before separation of serum and plasma: implications to Phi determination

2019 ◽  
Vol 57 (4) ◽  
pp. 521-531 ◽  
Author(s):  
Ruggero Dittadi ◽  
Aline S.C. Fabricio ◽  
Giulia Rainato ◽  
Edoardo Peroni ◽  
Fulvio Di Tonno ◽  
...  
Keyword(s):  
Whole Blood ◽  
Room Temperature ◽  
Specific Antigen ◽  
Free Psa ◽  
Glass Tubes ◽  
Edta Plasma ◽  
Total Psa ◽  
Clot Activator ◽  
Over Time

Abstract Background [-2]proPSA seems to outperform free/total prostate-specific antigen (PSA) ratio in prostate cancer diagnosis. However, [-2]proPSA stability remains an underestimated issue. We examined [-2]proPSA stability over time in whole blood before separation of serum and plasma and its implications for prostate health index (Phi) determination. Total PSA (tPSA) and free PSA (fPSA) stabilities were also assessed. Methods Blood was drawn from 26 patients and separated in two tubes for plasma (K2EDTA and K2EDTA plus protease inhibitors – P100) and one for serum (clot activator plus gel separator). Tubes were stored at room temperature before centrifugation 1, 3 and 5 h for serum and EDTA plasma or 1 and 5 h for P100 plasma. To investigate the influence of gel separator on markers’ stability, blood was collected from 10 patients in three types of tubes to obtain serum: tubes with clot activator plus gel separator, with silica particles or glass tubes. Biomarkers were assayed with chemiluminescent immunoassays. Results [-2]proPSA and Phi levels significantly and progressively increased over time in serum (+4.81% and +8.2% at 3 h; +12.03% and +14.91% at 5 h, respectively, vs. 1 h; p<0.001). Conversely, [-2]proPSA levels did not change in plasma (EDTA or P100). tPSA levels did not change over time in serum or plasma, whereas fPSA decreased in serum. All markers were higher in plasma than in serum at any time point. This difference did not seem to be attributable to the use of gel for serum preparation. Conclusions EDTA prevented spurious in vitro modifications in PSA-related isoforms, confirming that a stabilized blood sample is a prerequisite for [-2]proPSA measurement and Phi determination.

20–25% Lower Concentrations of Total and Free Prostate-Specific Antigen (PSA) after Calibration of PSA Assays to the WHO Reference Materials – Analysis of 1098 Patients in Four Centers

2009 ◽  
Vol 24 (2) ◽  
pp. 65-69 ◽  
Author(s):  
Carsten Stephan ◽  
Chris Bangma ◽  
Giulio Vignati ◽  
Georg Bartsch ◽  
Michael Lein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
World Health ◽  
Test Results ◽  
Misleading Information ◽  
Free Psa ◽  
Total Prostate Specific Antigen ◽  
Health Organization ◽  
Independent Cohort

Aim To examine the potential clinical implications of the recalibration of total prostate-specific antigen (PSA) and free PSA (fPSA) assays to the World Health Organization (WHO) standard materials. Material and methods Data from 1098 patients with or without clinically detected prostate cancer (PCa) from four independent cohort studies were compared using commercial assays calibrated to the traditional Hybritech® PSA (PSA-Hyb) and fPSA (fPSA-Hyb) standards and to the WHO 96/670 (PSA-WHO) and 96/668 (fPSA-WHO) standards. The Access® Immunoassay System (Beckman Coulter, Inc.) was used in all studies. Results All studies showed 20% to 25% lower PSA and fPSA test results with the WHO-standardized assays. No significant change in %fPSA (fPSA/PSA × 100) was observed. Continuing to use the traditional clinical PSA cutoffs obtained with the Hybritech standard after changing to the PSA-WHO standard could result in up to one-third of prostate cancer cases being missed. Conclusions: Manufacturers should fully inform laboratories about a calibration change and its clinical impact. Laboratory reports for PSA measurements should indicate the assay's manufacturer and which calibration standard was used to avoid misleading information concerning PCa risk

scholarly journals The Weight of HLA-DPA1 rs3077 Single Nucleotide Polymorphism in Prostate Cancer, a Multicenter Study

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Mohammed Jayed Alenzi ◽  
Amany A. Ghazy ◽  
Diaa-Eldin Taha
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Serum Levels ◽  
Arab Countries ◽  
Control Group ◽  
Single Nucleotide ◽  
Genetic Transmission ◽  
Free Psa ◽  
Protective Allele ◽  
Total Prostate Specific Antigen

Prostate cancer (PCa) has almost the highest genetic transmission that mimics an autosomal dominance hereditary pattern of cancers in some families. Its incidence in Arab countries was reported to be steadily increasing. Aim. To determine the relevance of HLA-DPA1 rs3077 (A/G) SNP with prostate cancer’s risk and/or severity. Subjects and Methods. Forty PCa patients and forty age matched patients with benign prostatic hyperplasia (BPH), as a control group, were enrolled in the study. Serum levels of urea, creatinine, total prostate-specific antigen (PSA), and free PSA were measured. PSA ratio was determined as well. Genotyping of HLA-DPA1 rs3077 (A/G) SNP was done using real-time PCR. Results. The measured lab parameters, except free PSA, were significantly higher among PCa patients in comparison to controls ( P < 0.001 ∗ ). Moreover, PSA ratio was significantly high among PCa patients ( P < 0.001 ∗ ). HLA-DPA1 rs3077 GG genotype was more frequent in PCa patients and the associated OR was 2.546 ( P = 0.059 ), while AA genotype was more frequent in the control group and the associated OR was 0.145 ( P = 0.081 ). Frequency of G allele was higher among PCa patients than the control group while A allele frequency was significantly decreased ( P = 0.034 ∗ ) (protective allele). On multivariate analysis, there is no significant correlation found between HLA-DPA1 rs3077 SNP and PSA ratio (OR = 4.5, 95% CI = 1.2–17.4, P = 0.856 ). Conclusion. HLA-DPA1 rs3077 G allele could be a risk factor for prostate cancer. However, HLA-DPA1 rs3077 SNP has no relation to PCa severity.

scholarly journals Performance of free prostate-specific antigen ratio in differentiating between prostatic cancer and benign prostatic lesions at a referral hospital in South Africa

2018 ◽  
Vol 60 (4) ◽  
pp. 54
Author(s):  
Boitumelo Phiri-Ramongane ◽  
Ayeaye Khine
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Total Population ◽  
Specific Antigen ◽  
Male Population ◽  
Free Psa ◽  
Total Prostate Specific Antigen ◽  
Good Discriminator ◽  
Male Patients ◽  
Current Screening

Background: Prostate cancer is a leading cause of morbidity and mortality in our male population, thus screening initiatives will help to improve outcomes. The current screening marker, total prostate-specific antigen (PSA), is not prostate cancer specific. The development of percentage free PSA (%FPSA) has largely improved the detection of prostate cancer.Objectives: To assess the performance of %FPSA ratio at the 25% cut-off and its ability to distinguish between prostate cancer and benign prostatic lesions.Methods: This was a retrospective study conducted on male patients with total prostate-specific antigen values 10 ng/ml and with prostate histology results. Male patients with total prostate-specific antigen between 4 and 10 ng/ml had their free prostate-specific antigen determined together with the calculation of the free prostate-specific antigen ratio. The ratio was then correlated with prostate histology results to determine the presence of prostate cancer at the cut-off ratio of 25%.Results: Prostate cancer was detected in 28 (21.37%) patients out of the total population of 131. Ninety-two patients had a FPSA ratio of 25%, 22 (22.8%) of whom were found to have prostate cancer. Notably the sensitivity and specificity were found to be 86% and 27% respectively, with a positive predictive of value of 21% at this cut-off.Conclusions: The study demonstrates a %FPSA ratio of 25% not to be a good discriminator between prostatic cancerous and benign lesions. It is thus recommended that a prostate biopsy should be done based on clinical examination findings rather than the level of total prostate specific antigen from 0–10 ng/ml or %FPSA ratio.

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