PSA Isoforms Research Articles

P2PSA-associated parameters are significant predictors of reclassification of first-year protocol biopsy on active surveillance for early-stage prostate cancer patients: From the PRIAS-JAPAN study.

153 Background: 44 Japanese institutions have joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study as PRIAS-JAPAN. As an side study, PRIAS-JAPAN investigates the usefulness of [-2] proPSA (p2PSA), a precursor of PSA, as a predictive marker for the reclassification during active surveillance patients. In this study, we aimed to evaluate the usefulness of p2PSA related parameters to predict the reclassification of first year protocol biopsy (1yr PBx). Methods: 19 institutions participated in this side study which started in January 2013. All participants were eligible for PRAIS inclusion criteria. These patients were required to receive blood sampling on every visit and protocol biopsy after inclusion. PSA and PSA isoforms (free-PSA, p2PSA) were measured in serum samples and parameters (%free-PSA, %p2PSA, phi) were also calculated. Mann-Whitney U test was used to compare continuous variables between reclassification and non-reclassification groups. Fisher's exact test and Chi-squared test with yates' continuity correction were used for categorical variables. Multivariable logistic regression models were used to predict the risk of reclassification. To assess the predictive power for reclassification, we plotted ROC curves and calculated the AUC. Decision curve analysis (DCA) was used to evaluate whether adding variables to the baseline (age, PSA, prostate volume) model would yield net clinical benefit. Results: From January 2013 to July 2017, this study enrolled 237patients. 99 patients were excluded for the reason of discontinuation of AS, non-adherence of protocol blood sampling and rejection of biopsy. 138patients were able to analyzed PSA, PSA isoforms and its parameters at the time of inclusion and 1yr PBx. Patients who showed reclassification were significantly higher level of %p2PSA at inclusion and %p2PSA and phi just before 1yr PBx. Multivariate analyses showed %p2PSA at inclusion (p= 0.04), %p2PSA (p= 0.01) and Phi (p= 0.008) before 1yr PBx were statistically significant predictors of reclassification at 1yr PBx. ROC analysis revealed that %p2PSA before 1yr PBx (AUC 0.674) and phi before 1yr PBx (AUC 0.669) were a significant discriminant factor in predicting reclassification. DCA analysis showed that phi before 1yr PBx had a highest net benefit in the range of clinically plausible risk threshold (10–40%). Conclusions: %p2PSA and Phi before 1yr PBx have good prediction power and phi is a most useful indicator of clinical decision making about active surveillance. Clinical trial information: UMIN 000009876.

PD48-08 THE ISOPSA ASSAY IS SENSITIVE FOR BIOPSY-IDENTIFIED CRIBRIFORM PATTERN 4 GLANDS AND INTRADUCTAL CARCINOMA OF THE PROSTATE

INTRODUCTION AND OBJECTIVE:IsoPSA is a novel structure-based serum assay that measures the relative concentration of PSA isoforms altered by disrupted cellular processes. IsoPSA-based early detecti...

PROSTATE-SPECIFIC ANTIGEN AND ITS MOLECULAR FORMS IN BLOOD SERUM OF HEALTHY WOMEN AND WOMEN WITH BREAST DISEASE

The purpose of the study was to provide data on the sources of prostate-specific antigen (Psa) in women, as well as on serum Psa levels in healthy women and in women with benign and malignant breast cancer. Material and methods. We analyzed 50 publications available from PubMed, Medline, Google scholar concerning non-prostatic sources of Psa and its use as a serum tumor-associated marker for benign and malignant breast tumors. Results. In our study, we focus on the recent findings on non-prostatic sources and regulation of Psa synthesis in women as well as on changes in serum concentrations of this marker in patients with benign and malignant breast tumors. Various Psa isoforms (total Psa and free Psa) and free/total ratio for the detection of breast cancer and the assessment of treatment response and early detection of breast cancer recurrence were analyzed. Conclusion . the results obtained highlight the value of the assessment of Psa isoforms for early detection, prediction of therapy response and detection of breast cancer relapse. However, further studies are needed to identify the role of Psa isoforms in the diagnosis and monitoring of breast cancer patients.

ProPSA and the Prostate Health Index as predictive markers for aggressiveness in low-risk prostate cancer-results from an international multicenter study.

One of the major challenges in prostate cancer (PCa) treatment is distinguishing insignificant PCa from those forms that need active treatment. We evaluated the impact of PSA isoforms on risk stratification in patients with low-risk PCa as well as in active surveillance (AS) candidates who underwent radical prostatectomy. A total of 112 patients with biopsy confirmed Gleason score (GS) 6 PCa of four different international institutions were prospectively enrolled in the study. Blood withdrawal was performed the day before radical prostatectomy. In addition, patients were classified according to the EAU and NCCN criteria for AS candidates. PSA, free PSA (fPSA) and proPSA were measured using dual monoclonal antibody sandwich immunoassays. In addition, the Prostate Health Index (PHI=proPSA/fPSA × √PSA) was calculated. Final histology of the radical prostatectomy specimens was correlated to PSA, its isoforms and PHI. Serum proPSA levels were significantly elevated in those patients with an upgrade in final histology (GS⩾7). In addition, higher proPSA levels were predictive for extraprostatic extension (⩾pT3a) as well as for positive surgical margins. Interestingly, PHI had an even higher predictive power when compared with proPSA alone concerning GS upgrading, extraprostatic extension and surgical margins in both the total and the AS patient group. We showed in a multicenter study that proPSA is a valuable biomarker to detect patients with aggressive PCa in a cohort of GS 6 patients, who would benefit from active tumor therapy. Combining proPSA with the standard markers PSA and fPSA using PHI further increases the predictive accuracy significantly. Moreover, our data support the use of PHI for monitoring PCa patients under AS.

IsoPSA: Interim clinical performance evaluation of a novel structure-based biomarker for prostate cancer in a multicenter prospective trial for Gleason ≥ 7.

20 Background: We report results from an interim evaluation of IsoPSA, a novel structure-focused protein assay to assess potential discrimination of high-grade (Gleason≥7) from benign or low-grade (Gleason=6) patients. The assay produces a single quantitative parameter, K, describing the overall composition of complex PSA (cPSA) isoforms, using step partitioning of proteins into two aqueous phases. The ratio of the overall complex PSA concentrations in the two phases differentiates between the two patient cohorts. In this multicenter prospective trial we provide performance data compared with biopsy reports. Methods: 217 plasma samples were obtained from multiple clinical sites, collected within 30 days prior to prostate biopsy from patients with blood PSA between 2 and 44 ng/ml (mean 7.5) and frozen at -80 degC. IsoPSA was evaluated within 90 days following collection against 12 core TRUS biopsy results as the ‘gold standard’ comparator. The prevalence of high-grade patients in the sample cohort was 33%. Results: IsoPSA results are reported as risk probability using a logistic regression model combining IsoPSA, K and age as input parameters, calibrated with 118 samples. We denote two possible regions signifying cohorts with low and high risk for aggressive cancer. These results could effectively reduce the number of unnecessary biopsies by 53%, while identifying high risk patients who could benefit from biopsy. Conclusions: This study provides further supporting analysis for IsoPSA, a novel structure-focused assay for prostate cancer. A simple parsimonious statistical model further enhances clinical performance using the test parameter IsoPSA K, and age only. [Table: see text]

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients.PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness.In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

Serum marker %[-2]proPSA and the Prostate Health Index improve diagnostic accuracy for clinically relevant prostate cancer.

Serum samples from patients with prostate cancer (PCa) are measured routinely for total PSA (tPSA) and complexed PSA as a part of the diagnostic evaluation. In addition, a variety of molecular isoforms of the PSA molecule can be assayed, including free PSA (fPSA), %freePSA, [-2]proPSA, %[-2]proPSA and the new combined calculation, termed the Prostate Health Index (PHI), which is calculated using [-2]proPSA, fPSA and tPSA. The PHI was developed by Beckman Coulter immunoassays and is performed on Access-2- or DxI800-instruments. Numerous clinical studies have been conducted with the isoforms of PSA (fPSA, %fPSA, [-2]proPSA and %[-2]ProPSA) to test the PCa diagnosis and prognosis predictions, and to predict the need for rebiopsies 1. In addition to these various molecular isoforms of US Food and Drug Administration-approved clinical bioassays for PSA, several PSA-computed derivatives have also been developed to assess kinetics such as PSA velocity, PSA density and PSA doubling time, and all of these tests have been used to evaluate mostly prognostic events (i.e. disease progression, metastasis and death) in patients with PCa 2. In the recent publication by Boegemann et al. in BJUI 3, the PHI is calculated as ([-2]proPSA/fPSA) × √tPSA). The PHI has been investigated previously with regard to its use in the diagnosis and prognosis of PCa, and key findings have included its role in defining PCa tumour aggressiveness 1, 4, 5, its value in predicting active surveillance upstaging 6, 7, and its ability to predict the need for a rebiopsy 1. When authors decide that a new PSA test may be valuable in the management of PCa, they usually include historic PSA and PSA isoforms for statistically relevant comparisons. It is most gratifying, therefore, that Boegemann et al. studied a total of 769 men ≤ 65 years old, scheduled for initial or repeat prostate biopsy and that they were recruited from four test sites. Their in-depth analysis included total PSA as well as its isoforms, generating univariate analysis. Results for %[-2]proPSA and the PHI yielded similar areas under the curve (0.72 and 0.73, respectively) in all patients (P < 0.001). They also showed that the PHI had the best performance in predicting the initial biopsy (0.67 and 0.68, respectively) and repeat biopsy (0.79 and 0.78, respectively) results. To substantiate their observations, the authors tested several multivariate models using logistic regression and artificial neural network (ANN) methods. Both worked, and in multivariate analysis PHI was added to a base model that included age, prostate volume and DRE results, tPSA and %fPSA. The PHI was strongest in predicting PCa in all patients, at initial and repeat biopsy and for significant PCa (AUC 0.73, 0.68, 0.78 and 0.72, respectively). All results were strongly supported by decision-curve analysis tools for ANN and logistic regression modelling, as well as single variable analysis for the PHI, %fPSA, tPSA, ‘treat all’ and ‘treat none’ data. In summary, the multicentre study by Boegemann et al. assessed 769 men aged ≤ 65 years at their initial and repeat prostate biopsy diagnoses and %[-2]proPSA and PHI were shown to be the strongest predictors of biopsy outcome. The two multivariate prediction ANN models (BM-1 and BM-2) were shown to minimize the risk of missing clinically significant PCa, while reducing the number of unnecessary biopsies in men without PCa or potentially insignificant disease. Currently, evaluation of high-risk cancer is often based on genomic knowledge and has ~70–75% accuracy to offer personalized treatment regimens. The present manuscript achieved similar accuracy using the PHI and routine clinicopathological features to create models for PCa detection and repeat biopsy decision-making. Furthermore, many patients and their doctors choose definitive treatment that might be unnecessary and can cause incontinence and/or impotence. Active surveillance is an alternative option for very-low- to low-risk PCa cases using a minimal number of positive biopsy cores, PSA density ≥and tPSA ≥ 10 ng/mL for entry criteria 6, 7. Clearly, a PCa risk predictor containing the best biomarkers, including the PHI, will improve the accuracy in the management of patients on active surveillance. There is also a need at the pretreatment diagnostic step to determine whether the pathological stage (i.e. non-organ-confined status) of the tumour requires definitive treatment (i.e. surgery and/or irradiation), with or without adjuvant therapy. Hence, we will need the best clinicopathological quantitative medical imaging and histomorphological (molecular and histological) information at pretreatment stage to create new and more accurate nomograms or tables and have them validated. Ultimately, the patient requires risk models with an accuracy close to 100% to make treatment decisions safely and with confidence 8. None declared.

Abstract 1818: Analytical platform evaluation for quantification of ERG oncoprotein in prostate cancer using protein and mRNA detection methods

Abstract Current molecular tests that aid in the diagnosis of prostate cancer (PCa) are based on the detection of PSA and PSA isoforms (blood), overexpression of PCA3 (urine), and overexpression of AMACR (tissue) as biomarkers. The discovery of cancer specific fusion transcripts, which are detected in over 50% of prostate cancers, revolutionized the field. As such, the cancer specific TMPRSS2-ERG gene fusion drives the overexpression of the ERG oncoprotein. Based on this, we hypothesized that ERG protein may serve as a valuable biomarker and for which quantification methods can be applied for the diagnosis of prostate cancer. An antibody-free assay for ERG protein detection was developed based on PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry. We utilized TMPRSS2-ERG positive VCaP and TMPRSS2-ERG negative LNCaP cells to simulate three different sample types (cells, tissue, and post-DRE urine sediment) for evaluation. Recombinant ERG protein spiked into LNCaP cell lysates could be detected at levels as low as 20 pg by PRISM-SRM analysis. The sensitivity of the PRISM-SRM assay was approximately 10,000 VCaP cells in a mixed cell population model of VCaP and LNCaP cells. Interestingly, ERG protein could be detected in as few as 600 VCaP cells spiked into female urine, presumably due to more effective loading of ERG protein and the reduced sample complexity. In comparison the detection limit of the in-house enzyme-linked immunosorbent assay was 30 pg of recombinant ERG protein and 10,000 VCaP cells, while Western blot analysis demonstrated the detection of 195 pg of recombinant ERG protein and 10,000 VCaP cells in these two sample types, respectively. On the other hand, qRT-PCR exhibited a higher sensitivity, as TMPRSS2-ERG transcripts were detected in as few as 250 VCaP cells spiked into female urine, in comparison to NanoString methodologies which detected 10,000 VCaP cells in the same sample. In summary the data presented here suggest that qRT-PCR and PRISM-SRM platforms are highly sensitive in detecting TMPRSS2-ERG transcripts and proteins, respectively. Compared to other RNA (without preamplifcation step) and protein detection technologies, the PRISM-SRM assay has several significant advantages: it is not affected by RNA stability, it does not rely on a specific antibody, and it is ideal for isoform-specific detection with high multiplexing capability. Therefore, PRISM-SRM assays can be adapted to detect ERG protein in cells present in clinical specimens (e.g., tissue and urine), and cell-free ERG protein present in the blood sera, providing an opportunity for their use in the clinical setting for detection of ERG in prostate cancer patients and for defining appropriate treatment strategies. Citation Format: Jintang He, Athena Schepmoes, Anshu Rastogi, Shyh-Han Tan, Wusheng Yan, Wei Huang, Sreedatta Banerjee, Tujin Shi, Chaochao Wu, Thomas Fillmore, Yuqian Gao, Jacob Kagan, Sudhir Srivastava, Richard Smith, Wei-Jun Qian, David McLeod, Gyorgy Petrovics, Albert Dobi, Alagarsamy Srinivasan, Shiv Srivastava, Karin Rodland, Tao Liu, David Camp. Analytical platform evaluation for quantification of ERG oncoprotein in prostate cancer using protein and mRNA detection methods. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1818. doi:10.1158/1538-7445.AM2015-1818

Evaluation of Prostate-Specific Antigen Isoform p2PSA and Its Derivates, %p2PSA, Prostate Health Index and Prostate Dimension-Adjusted Related Index in the Detection of Prostate Cancer at First Biopsy: An Exploratory, Prospective Study

Objective: To confirm the accuracy of serum proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and Prostate Health Index (PHI) and to test the value of prostate dimension-adjusted related index p2PSA density (p2PSAD), %p2PSA density (%p2PSAD) and PHI density (PHID) in discriminating between patients with and without prostate cancer (PCa). Patients and Methods: This is a prospective cohort study of 275 patients with a total PSA (tPSA) of 2-10 ng/ml who underwent initial prostate biopsy. Multivariate logistic regression models were complemented by predictive accuracy analysis. Results: PCa was diagnosed in 31.2% of subjects. Median tPSA did not differ between groups, while PSA density (PSAD), percent free PSA (%fPSA), p2PSA, %p2PSA, PHI, p2PSAD, %p2PSAD and PHID (all p < 0.05) were different between men with and without PCa. Univariate accuracy analysis showed p2PSAD (area under the receiver-operating characteristic curve [AUC]: 0.71), %p2PSAD (AUC: 0.76) and PHID (AUC: 0.77) to be the most accurate predictors of PCa at biopsy, significantly outperforming tPSA (AUC: 0.54), PSAD (AUC: 0.68) and %fPSA (AUC: 0.59) (p ≤ 0.001). At multivariate logistic regression models, p2PSAD and PHID significantly increased the accuracy of the basal multivariate model (all p < 0.01). At 90% specificity, sensitivity for p2PSAD, %p2PSAD and PHID were 33.7, 43 and 40.7%, respectively. Spearman's rho coefficient analysis demonstrated a significant relationship between Gleason score, %p2PSA (r = 0.216, p = 0.046), PHI (r = 0.223, p = 0.039) and %p2PSAD (r = 0.205, p = 0.05). Conclusions: Considering patients suited for initial prostate biopsy by a tPSA range of 2-10 ng/ml, PSA isoforms were confirmed to be strong predictors of PCa. The prostate dimension-adjusted PSA isoforms have been shown to differentiate between patients with or without PCa, with an AUC of 0.71-0.77, p2PSAD offering a gain in accuracy with respect to tPSA, %fPSA and PSAD.

Prostate-specific Antigen/Solvent Interaction Analysis: A Preliminary Evaluation of a New Assay Concept for Detecting Prostate Cancer Using Urinary Samples

To provide preliminary clinical performance evaluation of a novel prostate cancer (CaP) assay, prostate-specific antigen/solvent interaction analysis (PSA/SIA) that focused on changes to the structure of PSA. Two-hundred twenty-two men undergoing prostate biopsy for accepted clinical criteria at 3 sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in institutional review board-approved study. Before transrectal ultrasound-guided biopsy, patients received digital rectal examination with systematic prostate massage followed by collection of urine. The PSA/SIA assay determined the relative partitioning of heterogeneous PSA isoform populations in urine between 2 aqueous phases. A structural index, K, whose numerical value is defined as the ratio of the concentration of all PSA isoforms, was determined by total PSA enzyme-linked immunosorbent assay and used to set a diagnostic threshold for CaP. Performance was assessed using receiver operating characteristic (ROC) analysis with biopsy as the gold standard. Biopsies were pathologically classified as case (malignant, n=100) or control (benign, n=122). ROC performance demonstrated area under the curve=0.90 for PSA/SIA and 0.58 for serum total PSA. At a cutoff value of k=1.73, PSA/SIA displayed sensitivity=100%, specificity=80.3%, positive predictive value=80.6%, and negative predictive value=100%. No attempt was made in this preliminary study to further control patient population or selection criteria for biopsy, nor did we analytically investigate the type of structural differences in PSA that led to changes in k value. PSA/SIA provides ratiometric information independently of PSA concentration. In this preliminary study, analysis of the overall structurally heterogeneous PSA isoform population using the SIA assay showed promising results to be further evaluated in future studies.

Place du (−2) proPSA comme outil diagnostique du cancer de la prostate

To this day, early diagnosis of prostatic cancer mainly lies on PSA dosage. The limits of this marker induce the developing of new and more performing diagnosis tols both in imaging, blood and urinary biomarkers. The authors study the role of pro PSA isoforms and particularly the −2 proPSA.

Moving towards high density clinical signature studies with a human proteome catalogue developing multiplexing mass spectrometry assay panels.

A perspective overview is given describing the current development of multiplex mass spectrometry assay technology platforms utilized for high throughput clinical sample analysis. The development of targeted therapies with novel personalized medicine drugs will require new tools for monitoring efficacy and outcome that will rely on both the quantification of disease progression related biomarkers as well as the measurement of disease specific pathway/signaling proteins.The bioinformatics developments play a key central role in the area of clinical proteomics where targeted peptide expressions in health and disease are investigated in small-, medium- and large-scaled clinical studies.An outline is presented describing applications of the selected reaction monitoring (SRM) mass spectrometry assay principle. This assay form enables the simultaneous description of multiple protein biomarkers and is an area under a fast and progressive development throughout the community. The Human Proteome Organization, HUPO, recently launched the Human Proteome Project (HPP) that will map the organization of proteins on specific chromosomes, on a chromosome-by-chromosome basis utilizing the SRM technology platform. Specific examples of an SRM-multiplex quantitative assay platform dedicated to the cardiovascular disease area, screening Apo A1, Apo A4, Apo B, Apo CI, Apo CII, Apo CIII, Apo D, Apo E, Apo H, and CRP biomarkers used in daily diagnosis routines in clinical hospitals globally, are presented. We also provide data on prostate cancer studies that have identified a variety of PSA isoforms characterized by high-resolution separation interfaced to mass spectrometry.

Vascular endothelial growth factor (VEGF) and prostate pathology

Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) > or = 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR) and respective 95% confidence intervals (95% CI) for the association between serum VEGF and different prostatic pathologies. Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3%), prostatitis (16.6%), and prostatic cancer (55.0%). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%: 0.64-3.26). In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.

1607: Longitudinal Evaluation of Molecular PSA Isoforms and Human Glandular Kallikrein 2 in Predicting Biochemical Failure following Radical Prostatectomy

1607: Longitudinal Evaluation of Molecular PSA Isoforms and Human Glandular Kallikrein 2 in Predicting Biochemical Failure following Radical Prostatectomy

Papel actual del antígeno prostático específico y otros marcadores en el diagnóstico del cáncer de próstata

To evaluate the current role of PSA as a diagnostic method for prostate cancer, as well as to analyze possible new markers. We perform a bibliographic review for PSA, and its molecular forms, as a marker to define the presence of prostate cancer. We review the factors related to PSA modifications, predictive models, or the current controversies about the usefulness of its cutpoint to define the risk of prostate cancer or the marker itself. We analyze possible new markers and the most interesting work lines in the development of new markers. We used MEDLINE for the bibliographic search. Available data confirm that PSA has a high sensitivity; although specificity is low, mainly in the < 10 ng/ml range, it may be increased with the use of various molecular isoforms, ratios or predictive models. Nevertheless, it is true that despite such studies it is difficult to increase specificity, so biopsies are reduced. Currently we have new markers, some of them already marketed, others in development, which seem to improve the specificity of PSA (isoforms, use of molecular biology). PSA is still the standard marker for the diagnosis of prostate cancer. It is important to improve the specificity; therefore we need new predictive models or new isoforms that help us to do a better selection of candidates for biopsy. There are various promising research lines with new markers, but there is not ideal substitute for PSA yet.

1286: The Relationship between PSA Isoforms and BPH-Related Prostate Volume at Baseline in the MTOPS Trial

1286: The Relationship between PSA Isoforms and BPH-Related Prostate Volume at Baseline in the MTOPS Trial

1658: Effects of Prostate Biopsy on PSA Isoforms in men With BPH and Cancer

You have accessJournal of UrologyTuesday, May 11, 2004, 1:00 - 3:00 pm1 Apr 20041658: Effects of Prostate Biopsy on PSA Isoforms in men With BPH and Cancer Leonard S. Marks, Stephen D. Mikolajczyk, Harry G. Rittenhouse, Harry J. Linton, Cindy L. Evans, Maria L. Macairan, and Shamim M. Baker Leonard S. MarksLeonard S. Marks More articles by this author , Stephen D. MikolajczykStephen D. Mikolajczyk More articles by this author , Harry G. RittenhouseHarry G. Rittenhouse More articles by this author , Harry J. LintonHarry J. Linton More articles by this author , Cindy L. EvansCindy L. Evans More articles by this author , Maria L. MacairanMaria L. Macairan More articles by this author , and Shamim M. BakerShamim M. Baker More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)38866-9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1658: Effects of Prostate Biopsy on PSA Isoforms in men With BPH and Cancer." The Journal of Urology, 171(4S), p. 438 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 438 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Leonard S. Marks More articles by this author Stephen D. Mikolajczyk More articles by this author Harry G. Rittenhouse More articles by this author Harry J. Linton More articles by this author Cindy L. Evans More articles by this author Maria L. Macairan More articles by this author Shamim M. Baker More articles by this author Expand All Advertisement PDF downloadLoading ...

Age-related reference ranges for complexed prostate-specific antigen and complexed/total prostate-specific antigen ratio: results from East Texas Medical Center Cancer Institute screening campaign

The East Texas Medical Center Cancer Institute conducted a regional prostate cancer screening campaign over a 3-year period from 1998 through 2000. Total prostate-specific antigen (tPSA), complexed PSA (cPSA), and cPSA/tPSA ratio (c/tPSA) values were determined. To better define prostate cancer in the population, we chose to determine age-based reference ranges for these PSA isoforms in apparently healthy men. Participants (N = 12,902) between the ages of 20 and 94 were screened and demographic information and serum tPSA and cPSA values were collected across 41 centers throughout East Texas. Men with an abnormal digital rectal examination, a follow-up biopsy indicating prostatic disease, or any clinical signs and symptoms of prostatic disease were excluded. Sera from 7541 evaluable men were tested with the Bayer Immuno 1 PSA and cPSA methods at East Texas Medical Center. The resulting PSA data were then stratified by decade of age to determine age-related reference ranges for each PSA species. The cPSA values increased across all age decades: 40 to 49 years, 1.45 ng/mL; 50 to 59, 1.92 ng/mL; 60 to 69, 2.49 ng/mL; and 70 to 79, 2.77 ng/mL (95th percentile). tPSA levels also increased with age: 1.81 ng/mL, 2.45 ng/mL, 3.17 ng/mL, and 3.57, respectively. Comparatively, the c/tPSA levels remained constant (0.87), regardless of age. The upper limits of tPSA and cPSA values reported here suggest that men should be screened using lower cutoff values than are currently in use. These limits may more accurately identify prostate cancer among otherwise healthy men.

Different stability of free and complexed prostate-specific antigen in serum in relation to specimen handling and storage conditions.

The effect of sample collection, storage conditions (time and temperature), and freeze-thaw cycles on the stability of free prostate-specific antigen (fPSA), PSA complexed with alpha1-antichymotrypsin (ACT-PSA), and total PSA (tPSA) in serum was studied. The analytes were quantified using immunoassays for tPSA and fPSA on the Elecsys system 2010 and a research assay for ACT-PSA on the ES system (Roche Diagnostics). The stability of the analytes was calculated as percentages of the values measured in samples 1 h after blood collection. When the samples were stored at 37 degrees C, at room temperature or at 4 degrees C, the stability of ACT-PSA was less impaired than that of fPSA. To avoid erroneous results in the determination of PSA isoforms and their corresponding ratios, serum samples should be preserved at 4 degrees C when the analysis is performed within 8 h after blood collection, or they should be stored at -80 degrees C if the analysis is not feasible during that period.

Molecular Forms of Prostate-specific Antigen in Malignant and Benign Prostatic Tissue: Biochemical and Diagnostic Implications

Patients with prostate cancer (PCa) show a lower ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in serum than patients with benign prostatic hyperplasia (BPH). The patterns of the intracellular PSA isoforms in malignant and benign prostatic tissue have been studied as potential molecular reasons for this phenomenon. Prostatic tissue samples were obtained after cystoprostatectomy from patients with bladder cancer (n = 10), from BPH patients (transurethral resection of the prostate, n = 10; adenomectomy, n = 10), and from the cancerous and noncancerous parts of the same prostates removed surgically by prostatectomy because of PCa (n = 20). PSA pattern was characterized by gel filtration, immunoblotting, and immunoassays for tPSA, fPSA, alpha(1)-antichymotrypsin-PSA (ACT-PSA), and complexed PSA (Bayer Immuno 1 assay). Comparisons were made with the PSA concentrations in serum. The major portion of tPSA in all tissue samples was fPSA; complexed PSA forms were <2%. Samples from cystoprostatectomy patients had the lowest and those from adenomectomy patients the highest values of tPSA and fPSA. PSA concentrations were lower in cancerous than in the noncancerous parts of the prostate. No significant correlations were found between tumor stage or grade and the amounts of tPSA, fPSA, and ACT-PSA in tissue. Tissue PSA values were not correlated with the serum PSA concentrations nor with the ratios fPSA/tPSA and ACT-PSA/tPSA in sera. The amounts of tPSA and the PSA isoforms in prostatic tissue explain neither the concentrations of tPSA and PSA isoforms in serum nor the behavior of the ratio fPSA/tPSA in patients with BPH and PCa.