Urinary Prostate-specific Antigen Research Articles

Quantification of Urinary Exosomal Prostate-Specific Antigen for the Diagnosis of Prostate Cancer Using Clinical Laboratory-Based Techniques: Protocol for a Case-Control Study.

Prostate cancer is the most common cancer in men and represents a major public health problem. The current method for the diagnosis or screening of prostate cancer is invasive and costly. There have been renewed and innovative studies searching for urinary biomarkers to aid in the diagnosis of prostate cancer, especially with technologies based on urinary exosomes. However, technologies based on urine exosomes usually need expensive machines such as an ultracentrifuge and they are difficult to standardize, which hinder their application in clinical laboratories. We have optimized and standardized the isolation of urinary exosomes with the precipitation method. We have found that urinary exosomal prostate-specific antigen (PSA) can be quantified by automatic Elecsys total PSA technique. In this study, our objective is to utilize urinary exosomes from prostate cancer for the development of a test to aid in its diagnosis. Exosomes from the prostate cancer cell line LNCaP was used to set up the technique. To analyze urine samples from patients, the methods include the collection of first-void urine using the Colli-Pee device, the isolation of urine exosomes using the optimized precipitation method, and the quantification of exosomal PSA by Elecsys total PSA. This will be a 2-year study. We will start including patients and controls in the last quarter of 2024. We expect the results to be published in the second quarter of 2027. This is the first study to quantify urinary exosomal PSA using the Elecsys total PSA technique for the diagnosis of prostate cancer. This study emphasizes techniques that are suitable for implementation in clinical laboratories, which will facilitate the application of urinary exosomes to simplify and improve the diagnosis and screening of prostate cancer. PRR1-10.2196/63551.

Multiplex Determination of Glycan Profiles on Urinary Prostate-Specific Antigen by Quartz-Crystal Microbalance Combined with Surface-Enhanced Raman Scattering.

Prostate cancer remains a major health concern, with prostate-specific antigen (PSA) being a key biomarker for its detection and monitoring. However, PSA levels often fall into a "gray zone", where PSA levels are not clearly indicative of cancer, thus complicating early diagnosis and treatment decisions. Glycosylation profiles, which often differ between healthy and diseased cells, have emerged as potential biomarkers to enhance the specificity and sensitivity of cancer diagnosis in these ambiguous cases. We propose the integration of two complementary techniques, namely quartz-crystal microbalance with dissipation (QCM-D) and surface-enhanced Raman scattering (SERS) to study PSA glycan profiles. QCM-D offers real-time operation, PSA mass quantification, and label-free detection with high sensitivity, as well as enhanced specificity and reduced cross-reactivity when using nucleic acid aptamers as capture ligands. Complementary SERS sensing enables the determination of the glycosylation pattern on PSA, at low concentrations and without the drawbacks of photobleaching, thereby facilitating multiplexed glycosylation pattern analysis. This integrated setup could retrieve a data set comprising analyte concentrations and associated glycan profiles in relevant biological samples, which may eventually improve early disease detection and monitoring. Prostate-specific antigen (PSA), a glycoprotein secreted by prostate epithelial cells, serves as our proof-of-concept analyte. Our platform allows multiplex targeting of PSA multiplex glycosylation profiles of PSA at "gray zone" concentrations for prostate cancer diagnosis. We additionally show the use of SERS for glycan analysis in PSA secreted from prostate cancer cell lines after androgen-based treatment. Differences in PSA glycan profiles from resistant cell lines after androgen-based treatment may eventually improve cancer treatment.

Association between Bisphenol A and Prostate-Specific Antigen (PSA) among U.S. Older Males: National Health and Nutrition Examination Survey (NHANES), 2003-2012.

There is growing evidence indicating that environmental endocrine disruptors may influence the development of prostate cancer. Despite this, the connection between BPA and PSA levels is still not fully understood and appears intricate. In this study, we aimed to assess the link between BPA exposure and PSA levels using data from the NHANES database. We conducted a weighted linear regression, logistic regression analysis, natural cubic spline (NCS), subgroup analysis, and interaction analysis on 2768 participants. Urinary BPA was considered the independent variable, while PSA was the dependent variable. In the study, the average age of the participants selected was 62.70 years (±12.93). Age was negatively correlated with BPA, while PSA and BMI were positively correlated with BPA concentration (all of the p-value < 0.05). In the fully adjusted model, the weighted linear and logistic regression results showed that BPA was positively correlated with PSA and prostate cancer. NCS analysis results show that BPA and PSA have a non-linear relationship. Sensitivity and subgroup analyses showed similar results. In addition, there were interactions between BPA and age, PIR, education, HbA1c, high-density lipoprotein, smoking status, and Diabetes. There was a positive correlation between urinary BPA and PSA in older American males, especially when the BPA concentration was higher than 4.46 ng/mL. In future practical applications of prostate cancer screening, it is crucial to focus on individuals aged 75 years and older, as well as those with a PIR between 0 and 1, non-Hispanic black, and other risk groups to provide reference values for the primary and secondary prevention of prostate cancer.

Association between urinary metals and prostate-specific antigen in aging population with depression: a cross-sectional study

ObjectiveThis study aims to investigate the impact of depression and urinary metals on Prostate-Specific Antigen (PSA).MethodsAnalysis was conducted on 1901 samples collected from the National Health and Nutrition Examination Survey (NHANES) database between 2001 and 2010. Analytical methods included stepwise multiple linear regression (MLR) analysis of the overall population’s urinary metals and PSA relationship, analysis of urinary metals and PSA relationship in older adults and BMI subgroups, analysis of urinary metals and PSA relationship in the depressed population, and restricted cubic spline (RCS) analysis. A significance level of p &amp;lt; 0.05 was considered statistically significant.ResultsIn the stepwise multiple linear regression, beryllium (Be) showed a dose–response association with PSA (third quartile: β = 0.05, 95%CI (0.02, 0.09); fourth quartile: β = 0.07, 95%CI (0.02, 0.12), p trend = 0.048). Subgroup analysis indicated that in individuals aged &amp;gt;60, Be at Q4 level [β = 0.09, 95%CI (0.05, 0.21)] exhibited a dose–response correlation with PSA. In the population with 25 ≤ BMI &amp;lt; 30, Be might more significantly elevate PSA, with Q4 level having a pronounced impact on PSA levels [β = 0.03, 95%CI (0.02, 1.27)]. In the depressed population, urinary cadmium (Cd) levels showed a significant positive dose–response relationship, with Q4 level of Cd having the maximum impact on PSA [β = 0.3, 95%CI (0.09, 0.49)].ConclusionIndividuals exposed to beryllium (Be), especially the older adults and overweight, should monitor their PSA levels. In depressed patients, cadmium (Cd) levels may further elevate PSA levels, necessitating increased monitoring of PSA levels among males.

MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER Indu Kohaar, Yuefan Wang, Tung-Shing Mamie Lih, Naseruddin Höti, Lori Sokoll, Gregory Chesnut, Gyorgy Petrovics, and Hui Zhang Indu KohaarIndu Kohaar More articles by this author , Yuefan WangYuefan Wang More articles by this author , Tung-Shing Mamie LihTung-Shing Mamie Lih More articles by this author , Naseruddin HötiNaseruddin Höti More articles by this author , Lori SokollLori Sokoll More articles by this author , Gregory ChesnutGregory Chesnut More articles by this author , Gyorgy PetrovicsGyorgy Petrovics More articles by this author , and Hui ZhangHui Zhang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is predominantly indolent disease with a small fraction of patients undergoing metastatic progression. Therefore, it is critical to identify non-invasive diagnostic markers for the early detection of an aggressive PCa subtype. We hypothesized that non-invasive pre-digital rectal examination (pre-DRE) urine specimens harbor molecular signatures of aggressive PCa, which can help in the clinical management of the disease. Previously, we had systematically evaluated urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) using post-DRE urine specimens. The goal of the study is to explore the potential of using pre-DRE urine specimens for detecting AG-CaP and validate the post-DRE findings. METHODS: This is a retrospective case cohort study based on 154 pre-DRE urine specimens collected by the Center for Prostate Disease Research under an institutional review board approved protocol from men undergoing diagnostic biopsy. We performed an optimized quantitative mass spectrometric analysis to evaluate the association of markers with aggressive PCa at diagnosis. The cohort comprised 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score=6), and 65 patients with AG-PCa (Gleason score 7 or above). Targeted analyses of AG-PCa-associated glycoproteins previously identified in post-DRE urine samples were also applied to validate the post-DRE findings in non-DRE specimens. Data-independent acquisition mass spectrometry (DIA-MS) analysis was performed for glycosite-containing peptides. Fisher exact and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively and logistic regression was evaluated using receiver operating characteristic (ROC) analysis for the urinary markers and marker panels. RESULTS: Urinary prostatic acid phosphatase (ACPP), CD97 antigen (CD97), and prostate-specific antigen (PSA) levels in pre-DRE specimens were associated with patients with AG-PCa compared to cancer-negative and non-AG-PCa. The analysis confirmed three of the previously reported post-DRE urinary glycoproteins and identified three new AG-PCa-associated glycoproteins including Fibrillin 1 (FBN1), Vitronectin (VTN) and Hemicentin 2 (HMCN2). A multi-marker panel composed of urinary PSA, VTN, HMCN2, CD97 achieved an AUC of 0.78 (p=2.69 × 10-9) for distinguishing AG-PCa from cancer-negative & Gleason 6. Analysis of differentially abundant glycopeptides in pre- and post-DRE samples showed that compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas immune cell-related proteins were enriched in post-DRE urine samples. CONCLUSIONS: Comparisons between post-DRE and pre-DRE urine specimens for glycoproteins have shown that pre-DRE samples hold promise for a non-invasive and simple early option for AG-PCa detection in patients. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant prostate cancer. Source of Funding: NCI/EDRN IAA No. ACN 17005-001-0000011 (Gregory Chesnut) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e545 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Indu Kohaar More articles by this author Yuefan Wang More articles by this author Tung-Shing Mamie Lih More articles by this author Naseruddin Höti More articles by this author Lori Sokoll More articles by this author Gregory Chesnut More articles by this author Gyorgy Petrovics More articles by this author Hui Zhang More articles by this author Expand All Advertisement PDF downloadLoading ...

Urinary marker panels for aggressive prostate cancer detection

Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future.

Methylated DNA markers in urine aid in the selective identification of patients with prostate cancer as well as clinically significant pathology.

5091 Background: Controversy surrounding prostate-specific antigen (PSA) based screening for prostate cancer (PCa) highlights the need for non-invasive assays that better discriminate patients with and without clinically significant prostate cancer (csPCa). Such distinction avoids overtreatment in patients with absent or indolent disease while capturing pathology that would derive benefit from intervention. We analyzed the presence of specific methylated DNA markers (MDMs) within urine samples of patients with biopsy proven PCa and assessed the ability to discriminate these patients from healthy controls with no clinical suspicion for PCa. Methods: 24 healthy volunteers with no clinical suspicion for PCa were age-matched to 24 patients with biopsy-confirmed disease across all Gleason scores. Urine collected from subjects was centrifuged with the cell-free supernatant analyzed in a blinded fashion for methylation signal within specific DNA sequences across 14 genes ( HES5, ZNF655, ITPRIPL1, MAX.chr3.193, SLCO3A1, CHST11, SERPINB9, WNT3A, KCNB2, GAS6, AKR1B1, MAX.chr3.727, GRASP, ST6GALNAC2) by target enrichment long-probe quantitative-amplified signal assays. A patient was considered to have a positive MDM panel if any individual marker exceeded the corresponding100% specificity cut-off value (overall MDM panel specificity of 100%). MDM panel positivity was used to evaluate the sensitivity for distinguishing patients with PCa (any Gleason score) from controls as well as discriminate csPCa cancers from PCa Gleason 6. Results: Median age of healthy controls and PCa patients was 70 years (IQR 67-72) and 65 years (IQR 61-71), respectively. Median PSA was 6.4 (IQR 4.9-9.0) among PCa patients, including median PSA of 5 (IQR 4.0-6.1) for Gleason 6, and 7.8 (IQR 5.1-9.2) for Gleason ≥7 disease. Gleason 6, Gleason 7, and Gleason 8+ cancer was noted in 8, 10, and 6 patients, respectively. Utilizing an overall specificity cut-off of 100% for discriminating normal controls from PCa cases across the MDM panel revealed an overall sensitivity of 83% (95% CI: 63-95%) for detection of PCa (6 of 8 Gleason 6, 9 of 10 Gleason 7, 5 of 6 Gleason 8+) and 88% (95% CI: 62-98%) for csPCa (Gleason ≥ 7). When considering a 100% specificity threshold for controls and Gleason 6 patients, the sensitivity the MDM panel was 69% (95% CI: 41-89%) for csPCa (6 of 10 Gleason 7, 5 of 6 Gleason 8+). Conclusions: We describe a panel of 14 MDMs within urine that offer high specificity and sensitivity for detection of prostate cancers as well as selective identification of clinically significant disease states. Prospective comparison between urine MDMs and PSA blood testing is necessary to discern the differential clinical impact of each screening methodology.

Integrated workflow for urinary prostate specific antigen N-glycosylation analysis using sdAb partitioning and downstream capillary electrophoresis separation

Prostate cancer represents the second highest malignancy rate in men in all cancer diagnoses worldwide. The development and progression of prostate cancer is not completely understood yet at molecular level, but it has been reported that changes in the N-glycosylation of prostate-specific antigen (PSA) occur during tumor genesis. In this paper we report on the development and implementation of a high-throughput capillary electrophoresis based glycan analysis workflow for urinary PSA analysis. The technology utilizes selective, high yield single domain antibody based PSA capture, followed by preconcentration and capillary electrophoresis coupled with laser-induced fluorescence detection, resulting in high resolution N-glycan profiles. Urinary PSA glycan profiles were compared to a commercially available PSA standard revealing differences in their α2,3- and α2,6-sialylated isomers, proving the excellent selectivity of the suggested workflow. This is important as sialylation classification plays an important role in the differentiation between indolent, significant and aggressive forms of prostate cancer.

Association between pyrethroids and prostate endpoints; stratified according to renal function

BackgroundPyrethroids, one of the most commonly used pesticide classes, are considered to be selectively toxic toward insects rather than toward humans. However, there are accumulating data about pyrethroids toxicity in humans, especially sex organs. Thus, we investigated whether pyrethroids affected reproductive organs, especially the prostate gland. MethodsWith 1305 subjects who participated in the National Health and Nutrition Examination Survey, several measurements were performed: 3-phenoxybenzoic acid (3-PBA), a common metabolite of pyrethroids; prostate-specific antigen (PSA); and other covariates. Both logistic and linear regression analyses were performed after stratifying according to kidney function, which was evaluated based on the estimated glomerular filtration rate (eGFR). ResultsBy logistic regression, the ORs (95% CIs) of the highest quantile to the reference group for higher total PSA were 2.039 (1.018 – 4.084) in the total study population and 2.219 (1.083–4.548) in the high eGFR group. The ORs (95% CIs) of the highest quantile to the reference group for a lower PSA ratio were 1.979 (1.057 – 3.707) in the total study population and 2.101 (1.086 – 4.064) in the high eGFR group. By linear regression, a marginally significant positive correlation between urinary 3-PBA and total PSA (β ± Standard Error = 0.049 ± 0.026, p = 0.0712) and a significant positive correlation between urinary 3-PBA and PSA ratio (β ± Standard Error = 0.018 ± 0.007, p = 0.0191) among the low eGFR group were observed. ConclusionThis study showed that exposure to pyrethroids was associated with either increased levels of total PSA or alterations in the PSA ratio.

Profiling the proteoforms of urinary prostate-specific antigen by capillary electrophoresis – mass spectrometry

Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum concentrations of prostate-specific antigen (PSA) as an indicator of risk. However, this test has been widely criticized as it shows poor specificity and sensitivity. In order to improve early detection and diagnosis, several studies have investigated whether different PSA proteoforms are correlated to prostate cancer. Until now, studies and methodologies for the comprehensive characterization of PSA proteoforms from biofluids are scarce. For this purpose, we developed an intact protein assay to analyze PSA by capillary electrophoresis-electrospray ionization-mass spectrometry after affinity purification from patients' urine. Here, we determined six proteolytic cleavage variants. In regard to glycosylation, tri-, di-, mono- and non-sialylated complex-type N-glycans were found on non-cleaved PSA, as well as the non-glycosylated variant. The performance of the intact protein assay was assessed using a pooled sample, obtaining an inter-day variability of 15%. Furthermore, urinary patient samples were analyzed by intact protein analysis and a bottom-up approach (glycopeptide analysis). This combined approach revealed complimentary information on both levels, demonstrating the benefit of using two orthogonal techniques to provide a thorough profile of urinary PSA. SignificanceThe detection of clinically relevant prostate cancer requires a more specific and sensitive biomarker and, in this case, several PSA proteoforms may be able to aid or improve the current PSA test. However, a comprehensive analysis of the intact PSA proteoform profile is still lacking. This study investigated the PSA proteoforms present in urine and, in particular, determined the relative contribution of cleaved PSA and non-cleaved PSA forms to the total glycosylation profile. Importantly, intact protein analysis did not require further sample treatment before being measured by CE-ESI-MS. Furthermore, its glycosylation was also assessed in a bottom-up approach to provide complementary information. Overall, these results represent an important basis for future characterization and biomarker studies.

Detection of urinary prostate specific antigen by a lateral flow biosensor predicting repeat prostate biopsy outcome

This work describes the development and the application of a lateral flow biosensor for the detection of the prostate specific antigen in urine (uPSA). The biosensor allowed uPSA detection in 10 minutes with a limit of detection and a range of quantification respectively of 20 ng mL-1 and 37 – 420 ng mL-1, showing within and between-day coefficients of variation ≤ 13%. It showed 92% of accuracy and an almost perfect concordance with the reference electrochemiluminescence immunoassay method. The biosensor design provides the disappearance of the Test line signal at the cut-off concentration. This was achieved with a double layer sensing strategy, in which gold nanoparticles were functionalized with Staphylococcal protein A – a mediator – instead of anti-PSA antibody. This strategy allow making a fine-tune on the concentration of the specific antibody, obtaining an on/off switch of the Test line at the cut-off value. The cut-off value was also established in this work, based on the distribution of uPSA levels from 140 patients, who were suspected of prostate cancer and who underwent to first biopsy. The clinical application of the biosensor to predict repeat biopsy outcome in 28 patients showed sensitivity, specificity, positive and negative predictive values of 100%, 64%, 74% and 100%, respectively.

Urinary prostate-specific antigen and microseminoprotein-beta levels in men with and without prostate cancer: A prospective cohort study.

Introduction:The role of urinary proteomics in the diagnosis of prostate cancer (PCa) is undefined. Levels of urinary biomarkers such as prostate-specific antigen (PSA) and microseminoprotein-beta (MSMB) may differ between men with and without PCa. We tested this hypothesis using urine samples before and after digital rectal examination (DRE) in men with an indication for prostate biopsy.Materials and Methods:In an institutional ethics committee approved prospective cohort study, men with elevated PSA or a nodule on DRE underwent a pre- and post-DRE urine sample examination for urinary PSA and MSMB levels. Levels were compared between men who had PCa diagnosed on biopsy (Group A) and those with a negative biopsy (Group B).Results:Seventy-seven patients were recruited of whom 32 had PCa (Group A) and 45 had no cancer (Group B) on biopsy. The median (interquartile range) serum PSA was 49.6 (0.2–254) ng/ml. The median urine PSA (29.5 vs. 26.4 mg/dl) and MSMB (1.7 vs. 2.4 mg/dl) were similar in both groups at baseline. However, post-DRE, both these metabolites rose in Group B but not in Group A, resulting in significantly higher post-to-pre values in Group B versus Group A. The post-DRE urine PSA/MSMB ratio was also significantly different between the groups.Conclusions:Urinary PSA and MSMB rose significantly after DRE only in men without PCa. Post-DRE urine PSA, MSMB, and PSA/MSMB ratio can differentiate PCa from benign pathology in men with an indication for prostate biopsy.

Histopathology, pharmacotherapy, and predictors of prostatic malignancy in elderly male patients with raised prostate-specific antigen levels - A prospective study.

Background:Prostate cancer is the second most common cancer among adult men in the world, and the diagnosis requires biopsy. Prostate-specific antigen (PSA) test along with digital rectal examination (DRE) increases the detection rate of prostate cancer than DRE alone. The objective of this study was to correlate serum PSA level with histopathological diagnosis, identify the predictors of malignancy, and describe the pharmacotherapy of patients with serum PSA levels >4 ng/ml.Materials and Methods:This was a hospital-based observational study done among patients who presented with lower urinary tract symptoms and PSA levels >4 ng/ml who were planned to undergo prostatic biopsy. DRE followed by transrectal ultrasound (TRUS) assessment and guided sextant (6-core) prostatic biopsy was performed.Results:One hundred and four patients were screened and 87 were included. Nineteen patients were diagnosed with malignancy, and among them, eight had bone metastasis. Spearman's correlation coefficient between PSA and malignancy was 0.449 (P ≤ 0.001). Multivariate analysis suggested that the factors (adjusted odds ratio; 95% confidence interval; P value) such as increasing age (1.127; 1.013, 1.253; 0.027), nodular prostate (22.668; 4.655, 110.377; P < 0.001), and PSA (1.034; 1.004, 1.064; 0.024) were significant predictors of prostate cancer. All patients with benign prostatic hyperplasia were advised a combination therapy with 5-alpha reductase inhibitor and selective alpha-1 receptor antagonist while those with malignancy were prescribed androgen deprivation therapy with antiosteoporosis therapy.Conclusion:In elderly patients with raised PSA levels or suspicious DRE findings, TRUS-guided prostate is recommended to rule out malignancy and plan appropriate management.

Is Engrailed-2 (EN2) a truly promising biomarker in prostate cancer detection?

Purpose: Prostate-specific antigen (PSA) is a sensitive but unspecific marker for prostate cancer (PC) detection, which may result in harms including overdiagnosis and overtreatment. Therefore, the development of new markers is of absolute value. The urinary level of engrailed-2 (EN2) protein has been recently suggested as a promising PC biomarker, correlating with tumour volume and stage. This study evaluated EN2 and its potential use in clinical practice.Materials and methods: Urinary EN2 was assessed by different commercially available enzyme-linked immunosorbent assay kits. The study sample included 90 patients with clinically localized PC compared to 30 healthy controls, and a group of 40 patients indicated for prostate biopsy due to an elevated PSA level where both pre- and post-digital rectal examination urine samples were collected.Results: No statistical difference between the patient group and the control group was obtained in all measured variables. There was no significant correlation between urinary EN2 and serum PSA, tumour staging and grading. Attentive DRE did not lead to significant changes of urinary EN2 or impact on its predictive power.Conclusions: Our results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice.

Prostate Cystadenocarcinoma: A Rare Cystic Epithelial Lesion in an Unusual Clinical Setting

Abstract Introduction Cystic tumors of prostate are rare and their clinicopathologic significance remains to be defined. The tumors present with either obstructive urinary symptoms or elevated serum prostate-specific antigen (PSA). Here we report a multilocular cystadenocarcinoma in a patient without significant urologic symptoms. Case Report A 71-year-old male with prior abnormal prostate biopsy, 6 years previously (unknown pathology), was referred for prekidney transplant workup. His symptom of oliguria and proteinuria was associated with end-stage renal disease without any obstructive urinary symptoms. Serum PSA detected 5.5 ng/mL. Magnetic resonance imaging (MRI) of the pelvis demonstrated a multilocular cystic lesion measuring 6.2 × 4.6 cm, arising from the right peripheral zone of prostate. The patient underwent MRI-guided prostate needle biopsy. Histology of prostate biopsy revealed glands and cystic structures lined by cuboidal to columnar epithelial cells with basally located hyperchromatic nuclei, pseudostratification, and focal papillary architecture. The cyst wall was immunoreactive for Cam 5.2, NKX 3.1, and AMACR, while negative for PAX8 and 34BE12 and p63, suggesting a diagnosis of primary prostate cystadenocarcinoma. The patient underwent robotic prostatectomy. The resected specimen showed a soft periprostatic mass, 6.8 × 5.0 cm at the right posterolateral aspect. Cut sections showed multiple multilocular cysts, with papillary projections, involving the right posterior-lateral surfaces with extensive extraprostatic extension. Histology showed multilocular cysts with papillary lining. Immunohistochemical studies showed strong reactivity of the cyst lining for NKX3.1, AMACR, weak CDX-2, and absent 34be12, p63, and ERG reactivity. The microscopic and immunohistochemical evidence supported a diagnosis of prostate cystadenocarcinoma, stage pT3a with free resection margin. Conclusion Cystadenocarcinoma is a variant of prostate carcinoma associated with obstructive urinary symptoms and potential for locally advanced growth. This case and other published reports of prostate cystadenocarcinoma show histologic features similar to the ductal variant of prostate adenocarcinoma, and therefore we suggest to grade it as Gleason pattern 4. The current case of prostate cystadenocarcinoma was an incidental diagnosis in an asymptomatic patient with mildly elevated PSA (T1c).

Effects of Prostatic Artery Embolization on the Dynamic Component of Benign Prostate Hyperplasia as Assessed by Ultrasound Elastography: A Pilot Series.

To determine the effects of prostatic artery embolization (PAE) on prostaticelasticity as assessed by Ultrasound Elastography (US-E), as well as to describe the feasibility and role of US-E as a novel tool in both pre- and post-PAE evaluation. This is a prospective, single-center investigation that included eight patients undergoing PAE for treatment of lower urinary tract symptoms (LUTS) attributed to benign prostate hyperplasia (BPH). Baseline and 3-month follow-up evaluations were performed and included prostate-specific antigen (PSA), uroflowmetry, pelvic magnetic resonance imaging and clinical assessment using the International Prostate Symptom Score (IPSS) questionnaire and the IPSS-Quality of life (QoL) item. US-E with measurement of the prostatic Elastic Modulus (EM) was performed before PAE and at 1-month follow-up. After PAE, US-E showed a significant reduction of prostatic EM as assessed in kPa (33.14 vs. 47.24, - 29.8%, p = 0.002) and in m/s (3.75 vs. 4.63, - 19.0%, p < 0.001). Also, the transitional/peripheral zone ratio was significantly reduced by 45.36% (0.53 vs. 0.97, p < 0.05). All eight patients presented with significant LUTS improvement after PAE (p < 0.05 for IPSS, QoL, prostate volume, peak urinary flow rate and PSA). Findings described in this study suggest that PAE significantly reduces prostaticEM, leading to a positive effect on BPH dynamic component related to prostatic elasticity. Also, it features US-E as an additional tool for pre- and post-PAE evaluation, describing a novel indication for this technology.

Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins.

Biomarkers for effective early diagnosis and prognosis of prostate cancer are still lacking. Multiplexed assays for cancer-associated proteins could be useful for identifying biomarkers for cancer detection and stratification. Herein, we report the development of sensitive targeted mass spectrometry assays for simultaneous quantification of 10 prostate cancer-associated proteins in urine. The diagnostic utility of these markers was evaluated with an initial cohort of 20 clinical urine samples. Individual marker concentration was normalized against the measured urinary prostate-specific antigen level as a reference of prostate-specific secretion. The areas under the receiver-operating characteristic curves for the 10 proteins ranged from 0.75 for CXL14 to 0.87 for CEAM5. Furthermore, MMP9 level was found to be significantly higher in patients with high Gleason scores, suggesting a potential of MMP9 as a marker for risk level assessment. Taken together, our work illustrated the feasibility of accurate multiplexed measurements of low-abundance cancer-associated proteins in urine and provided a viable path forward for preclinical verification of candidate biomarkers for prostate cancer.

Method development of glycoprotein biomarkers for cancers.

Method development of glycoprotein biomarkers for cancers.

Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer

The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA.

Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile

AimNowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. We investigated if...