Benign Prostate Tissue Research Articles

Expressed prognostic biomarkers for primary prostate cancer independent of multifocality and transcriptome heterogeneity.

The majority of prostate cancer patients are diagnosed with multiple primary malignant foci. The distinct foci are exceptionally heterogeneous with regard to DNA mutations, but whether this is recapitulated at the transcriptome level remains unknown. In this study, inter- and intrafocal heterogeneity has been assessed by whole-transcriptome sequencing of 87 tissue samples from 23 patients with localized prostate cancer treated with radical prostatectomy. From each patient, multiple samples were taken from one or more malignant foci, in addition to one sample from benign prostate tissue. Transcriptomic profiles of different malignant foci from the same patient showed a similar level of heterogeneity as tumors from different patients. This applies to expression of genes, fusion genes, and somatic mutations. Within-patient pair-wise analyses identified expression patterns linked to ETS status and extraprostatic extension. A set of 62 genes were found with low intrapatient heterogeneity and high interpatient heterogeneity, retaining stable expression profiles across foci within the same patient. Among these, 16 genes are associated with biochemical recurrence in a separately published study and are therefore nominated as biomarkers with prognostic value regardless of which malignant focus is sampled. In conclusion, an extensive heterogeneity in multifocal prostate cancer is confirmed at the gene expression level. Diagnostic biomarkers were identified for ETS positive samples and samples from extraprostatic extensions. Finally, prognostic biomarkers independent of multifocal heterogeneity were found.

The Classification Power of Classical and Intra-voxel Incoherent Motion (IVIM) Fitting Models of Diffusion-weighted Magnetic Resonance Images: An Experimental Study.

This study aims at investigating the classification power of different b-values of the diffusion-weighted magnetic resonance images (DWI) as indicator of prostate cancer. This paper investigates several techniques for analyzing data from DWI acquired at a range of b-values for the purpose of detecting prostate cancer. In the first phase of experiments, we analyze the available data by producing two main parametric maps using two common models, namely: the intra-voxel incoherent motion (IVIM) model and the mono-exponential ADC model. Accordingly, we evaluated the benign/malignant tissue classification potential of several parametric maps produced using different combinations of b-values and fitting models. In the second phase, we utilized the maps that performed best in the first phase of experiments to design a machine learning-based computer-assisted diagnosis system for the detection of early stage prostate cancer. The system performance was cross-validated using data from 20 patients. On a fivefold cross-validation scheme, a maximum accuracy and an area under the receiver operating characteristic (AUC) of 90% and 0.978, respectively, was achieved by a system that uses ADC maps fitted using the mono-exponential model at 11 different b-values. The results suggest that the proposed machine learning-based diagnosis system is potentially powerful in differentiating between malignant and benign prostate tissues when combined with carefully generated ADC maps.

Cost-Effectiveness of Prostate Cancer Detection in Biopsy-Naïve Men: Ultrasound Shear Wave Elastography vs. Multiparametric Diagnostic Magnetic Resonance Imaging.

This exploratory study investigates the cost-effectiveness of ultrasound shear wave elastography (SWE) imaging in comparison to pre-biopsy multiparametric magnetic resonance imaging (mpMRI) in men with suspected prostate cancer. This research is motivated by the early evidence of the good performance of SWE in distinguishing cancerous from benign prostate tissues. We used a decision analysis model representing the care-pathways of men referred with a high prostate specific antigen (PSA) and/or abnormal digital rectal examination (DRE) in a UK setting from the payer’s perspective with results reported in 2016 GBP. We then appraised the cost-effectiveness of a novel approach based on SWE compared to the more conventional and widely practiced mpMRI-based approaches using data reported in the literature. Deterministic and probabilistic sensitivity analyses were used to address uncertainty regarding the parameter values utilised. Our exploratory results implied that SWE approach yielded an additional quality-adjusted life year (QALY) at the cost of GBP 10,048 compared to the standard mpMRI-based approach in the UK. This is lower than the official willingness to pay threshold of GBP 20,000 (the UK healthcare system guidelines) and is therefore a suitable replacement for the current practice. Sensitivity analyses confirmed the robustness of our results.

ARPC1B Is Associated with Lethal Prostate Cancer and Its Inhibition Decreases Cell Invasion and Migration In Vitro.

ARPC1B (Actin Related Protein 2/3 Complex Subunit 1B) has been found to be involved in platelet abnormalities of immune-mediated inflammatory disease and eosinophilia. However, its role in prostate cancer (PCa) has not been established. We characterized the role of ARPC1B in PCa invasion and metastasis and investigated its prognosis using in vitro cellular models and PCa clinical data. Higher immunohistochemistry (IHC) expressions of ARPC1B were observed in localized and castrate resistant PCa (CRPC) vs. benign prostate tissue (p < 0.01). Additionally, 47% of patients with grade group 5 (GG) showed high ARPC1B expression vs. other GG patients. Assessing ARPC1B expression in association with two of the common genetic aberrations in PCa (ERG and PTEN) showed significant association to overall and cause-specific survival for combined assessment of ARPC1B and PTEN, and ARPC1B and ERG. Knockdown of ARPC1B impaired the migration and invasion of PC3 and DU145 PCa cells via downregulation of Aurora A kinase (AURKA) and resulted in the arrest of the cells in the G2/M checkpoint of the cell cycle. Additionally, higher ARPC1B expression was observed in stable PC3-ERG cells compared to normal PC3, supporting the association between ERG and ARPC1B. Our findings implicate the role of ARPC1B in PCa invasion and metastasis in association with ERG and further support its prognostic value as a biomarker in association with ERG and PTEN in identifying aggressive phenotypes of PCa cancer.

Microbiota of the prostate tumor environment investigated by whole-transcriptome profiling

BackgroundWith over 350,000 estimated deaths worldwide in 2018, prostate cancer (PCa) continues to be a major health concern and a significant cause of cancer-associated mortality among men. While cancer in general is considered a disease of the human genome, there is a growing body of evidence suggesting that changes to the healthy microbiota could play a vital role in cancer development, progression, and/or treatment outcome.MethodsUsing a metatranscriptomic approach, we annotated the microbial reads obtained from total RNA sequencing of 106 prostate tissue samples from 94 PCa patients (discovery cohort). We investigated microbial dysbiosis associated with PCa by systematically comparing the microbiomes between benign and malignant tissue samples, between less vs. more-aggressive PCa, and between patients who had biochemical recurrence as opposed to those who did not. We further performed differential gene expression and cell type enrichment analysis to explore the host transcriptomic and cellular responses to selected microbial genera. A public dataset (GSE115414) of total RNA sequencing reads from 24 prostate tissue samples (8 benign and 16 malignant) served as the validation cohort.ResultsWe observed decreased species diversity and significant under-representation of Staphylococcus saprophyticus and Vibrio parahaemolyticus, as well as significant over-abundance of Shewanella in malignant as compared to benign prostate tissue samples in both the discovery (p < 0.01) and validation (p < 0.05) cohorts. In addition, we identified Microbacterium species (p < 0.01) to be significantly over-abundant in pathologically advanced T3 tumors compared to T2 in the discovery cohort. Malignant samples having high vs. low Shewanella counts were associated with downregulated Toll-like receptor signaling pathways and decreased enrichment of dendritic cells. Malignant samples having low vs. high V. parahaemolyticus counts were enriched for olfactory transduction and drug metabolism pathways. Finally, malignant samples were enriched for M1 and M2 macrophages as compared to benign tissue samples.ConclusionsThe results from this exploratory study support the existence of an important biological link between the prostate microbiota and PCa development/progression. Our results highlight Shewanella, V. parahaemolyticus, and Microbacterium sp. as interesting candidates for further investigation of their association with PCa.

MiR-378a inhibits glucose metabolism by suppressing GLUT1 in prostate cancer

Prostate cancer (PCa) is the fifth leading cause of cancer related deaths worldwide, in part due to a lack of molecular stratification tools that can distinguish primary tumours that will remain indolent from those that will metastasise. Amongst potential molecular biomarkers, microRNAs (miRs) have attracted particular interest because of their high stability in body fluids and fixed tissues. These small non-coding RNAs modulate several physiological and pathological processes, including cancer progression. Herein we explore the prognostic potential and the functional role of miRs in localised PCa and their relation to nodal metastasis. We define a 7-miR signature that is associated with poor survival independently of age, Gleason score, pathological T state, N stage and surgical margin status and that is also prognostic for disease-free survival in patients with intermediate-risk localised disease. Within our 7-miR signature, we show that miR-378a-3p (hereafter miR-378a) levels are low in primary tumours compared to benign prostate tissue, and also lower in Gleason score 8–9 compared to Gleason 6–7 PCa. We demonstrate that miR-378a impairs glucose metabolism and reduces proliferation in PCa cells through independent mechanisms, and we identify glucose transporter 1 (GLUT1) messenger RNA as a direct target of miR-378a. We show that GLUT1 inhibition hampers glycolysis, leading to cell death. Our data provides a rational for a new PCa stratification strategy based on miR expression, and it reveals that miR-378a and GLUT1 are potential therapeutic targets in highly aggressive glycolytic PCa.

Comparative Analysis of Proteomes and Phosphoproteomes in Patients with Prostate Cancer Using Different Surgical Conditions.

PurposeTo establish the standard of procedure in preparing benign and cancerous prostate tissues and evaluate the quality of proteomics and phosphoproteomics during transurethral resection of the prostate (TUR-P) with different surgical conditions.Materials and MethodsTUR-P tissue samples from three patients, two diagnosed with prostate cancer and one with benign prostatic hyperplasia, were each analyzed under three different conditions, based on differences in energy values, tissue locations, and surgical techniques. Global- and phosphorylated proteomic profiles of prostate tissues were analyzed by liquid chromatography-tandem mass spectrometry.ResultsA total of 6,019 global proteins and 4,280 phosphorylated peptides were identified in the nine tissues. The quantitative distributions of proteins and phosphorylation in tissues from the same patient were not affected by changes in the surgical conditions, but indirect relative comparisons differed among patients. Phosphorylation levels, especially of proteins involved in the androgen receptor pathway, important in prostate cancer, were preserved in each patient.ConclusionsProteomic profiles of prostate tissue collected by TUR-P were not significantly affected by energy levels, tissue location, or surgical technique. In addition, since protein denaturation of samples through TUR-P is rarely confirmed in this study, we think that it will be an important guide for tissue samples in castration resistant prostate cancer patients, where it is difficult to obtain tissue. This result is the first report about proteomic and phosphoproteomic results with TUR-P samples in prostate cancer and will be theoretical basis in protein analysis research with prostate cancer tissues.

Role of Genetic Variations in CDK2, CCNE1 and p27KIP1 in Prostate Cancer.

Our aim was to investigate possible influences of genetic variants in genes involved in the G1/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27KIP1)] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer. We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27KIP1 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27KIP1 was evaluated by quantitative real-time-polymerase chain reaction and western blotting in 44 prostate cancer tissues and 31 benign prostatic hyperplasia tissues. No association was found between CDK2 rs2069408, CCNE1 rs997669 or p27KIP1 rs2066827 polymorphisms and an increased risk of prostate cancer development. Higher CDK2 expression was more prevalent in those with rs2069408 GG genotype than in AA carriers (p>0.05). We also noted reduced p27KIP1 protein expression in those with the p27KIP1 G109 allele. No difference was observed for CCNE1 expression in relation to the risky genotype (CC). A significant association was detected between CCNE1 mRNA overexpression and development of higher-grade carcinomas (Gleason score >7, p<0.05). Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27KIP1, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.

RASAL2 suppresses the proliferative and invasive ability of PC3 prostate cancer cells.

The RAS protein activator like 2 (RASAL2) negatively regulates RAS proto-oncogene which is activated by high mutation rate in cancer. Thus, RASAL2 expression could potentially limit the function of RAS in prostate cancer (PCa). Genome-wide DNA methylation analysis demonstrated that RASAL2 is differentially hypermethylated in PCa tissues compared to benign prostate tissues. The PCR analysis of RASAL2 mRNA transcript showed differential expression in a panel of prostate cell lines with most PCa showing lower RASAL2 expression compared to benign prostatic epithelial cells. In PCa PC3 cells, the ectopic expression of RASAL2 significantly inhibited cell proliferation and invasion and induced an S phase plus G2/M phase cell cycle arrest. Ingenuity Pathway Analysis (IPA) demonstrated a cross talk between RASAL2 and TNFα, a key cytokine in immune signaling pathway that is relevant in PCa. Over-expression of RASAL2 downregulated TNFα expression whereas the knockdown of RASAL2 caused increased expression of TNFα. Taken together, our data demonstrates tumor suppressor role for RASAL2 in human PCa cells, despite increased RAS oncogenic activity. Our observation provides a new mechanistic insight of RASAL2 expression in aberrant Ras expression and immune signaling in PCa cells suggesting a potential novel therapeutic target for PCa.

Advanced glycation end-products (AGEs) are lower in prostate tumor tissue and inversely related to proportion of West African ancestry.

The metabolism of normal prostate relies on glycolysis, with prostate cancer having reduced glycolysis and increased aerobic metabolism. Advanced glycation end products (AGEs) accumulate in tissues as a result of age and glycolytic rate. Differential AGE levels were recently observed in prostate cancer tissues. Herein we sought to quantify AGEs in benign and cancer prostate tissue in a diverse cohort of patients. Levels of the AGE Nε-(carboxylethyl)lysine (CML) were quantified by immunohistochemistry (IHC) in a tissue microarray which consisted of 3 cores from tumor and 2 cores from benign areas from 118 patients (87 African American and 31 European American). Ancestry informative markers for African Ancestry were available for 79 patients. Epithelial and stromal areas were quantified separately using an E-cadherin mask. CML levels were compared with clinical grade group and ancestry by mixed linear effect models. Age, prostate-specific antigen (PSA) levels, body mass index (BMI), and hemoglobin A1C were included as covariates. CML levels were lower in areas of the tumor, for both epithelium and surrounding stroma, compared with benign, but did not significantly change with tumor grade group. Age, PSA levels, BMI, and hemoglobin A1C did not associate with CML levels. CML levels were inversely associated with the percentage of African Ancestry in all tissues. The low CML levels in cancer may reflect the reduced glycolytic state of the tissue. The inverse relationship between African Ancestry and CML levels in both benign and cancer areas suggests a state of reduced glycolysis. It is yet to be determined whether altered glycolysis and CML levels are bystanders or drivers of carcinogenesis.

A prostate cancer tissue specific spectral library for targeted proteomic analysis.

Prostate cancer is the most common cancer in males worldwide. Mass spectrometry-based targeted proteomics has demonstrated great potential in quantifying proteins from formalin-fixed paraffin-embedded (FFPE) and (fresh) frozen biopsy tissues. Here we provide a comprehensive tissue-specific spectral library for targeted proteomic analysis of prostate tissue samples. Benign and malignant FFPE prostate tissue samples were processed into peptide samples by pressure cycling technology (PCT)-assisted sample preparation, and fractionated with high-pH reversed phase liquid chromatography (RPLC). Based on data-dependent acquisition (DDA) MS analysis using a TripleTOF 6600, we built a library containing 108,533 precursors, 84,198 peptides and 9384 unique proteins (1% FDR). The applicability of the library was demonstrated in prostate specimens.

Novel role of prostate cancer risk variant rs7247241 on PPP1R14A isoform transition through allelic TF binding and CpG methylation.

Although previous studies identified numerous single nucleotide polymorphisms (SNPs) and their target genes predisposed to prostate cancer (PrCa) risks, SNP-related splicing associations are rarely reported. In this study, we applied distance-based sQTL analysis (sQTLseekeR) using RNA-seq and SNP genotype data from benign prostate tissue (n = 467) and identified significant associations in 3344 SNP-transcript pairs (P ≤ 0.05) at PrCa risk loci. We characterized a common SNP (rs7247241) and its target gene (PPP1R14A) located in chr19q13, an sQTL with risk allele T associated with upregulation of long isoform (P = 9.99E-7). We confirmed the associations in both TCGA (P = 2.42E-24) and GTEX prostate cohorts (P = 9.08E-78). To functionally characterize this SNP, we performed chromatin immunoprecipitation qPCR and confirmed stronger CTCF and PLAGL2 binding in rs7247241 C than T allele. We found that CTCF binding enrichment was negatively associated with methylation level at the SNP site in human cell lines (r = -0.58). Bisulfite sequencing showed consistent association of rs7247241-T allele with nearby sequence CpG hypermethylation in prostate cell lines and tissues. Moreover, the methylation level at CpG sites nearest to the CTCF binding and first exon splice-in (ψ) of PPP1R14A was significantly associated with aggressive phenotype in the TCGA PrCa cohort. Meanwhile, the long isoform of the gene also promoted cell proliferation. Taken together, with the most updated gene annotations, we reported a set of sQTL associated with multiple traits related to human prostate diseases and revealed a unique role of PrCa risk SNP rs7247241 on PPP1R14A isoform transition.

High-intensity focused ultrasound for the treatment of prostate cancer: assessing location of failure after focal therapy in prostate cancer and review of histological characteristics and clinicopathologic correlates after treatment—a 5-year experience

High-intensity focused ultrasound (HIFU) is a noninvasive treatment option used for localized prostate cancer or salvage surgery after failed radiation therapy. Histological changes in post-treatment needle biopsies are reviewed to better understand HIFU failures. Between 2016 and 2021, 50 patients with localized prostate cancer were enrolled and treated in this study. Of these, 10 patients underwent salvage therapy after radiation failure and 7 did not have post-treatment needle biopsies available for review and were excluded. Inclusion criteria included pathologically confirmed prostate cancer and clinical stage T1/T2 disease. We describe the histological changes in post-treatment needle biopsies as part of routine follow-up. Biopsies were examined for presence, distribution and extent of residual adenocarcinoma, Gleason score, and ablative tissue changes. A total of 33 patients underwent HIFU hemi-ablation treatment of localized prostate cancer as primary treatment with post-treatment biopsies available for review. The average mean age of the patients was 64 years (range, 52-81 years). The average PSA (prostate-specific antigen) level of the patients was 6.3ng/mL (range, 2.4-14.7ng/mL). The Gleason scores assigned in pretreatment prostate needle biopsies are as follows: 3 + 3 (1 case, 3%), 3 + 4 (21 cases, 64%), 4 + 3 (9 cases, 27%), and 4 + 4 (2 cases, 6%). In post-treatment needle biopsies, 33 cases (100%) showed variable degrees of fibrosis ranging from mild to moderate. Twenty-four of 33 cases (73%) showed necrosis usually associated with acute and/or chronic inflammation. Histological examination of benign glands revealed glandular heterogeneity including atrophy and basal cell hyperplasia. Eight cases (24%) had residual prostatic adenocarcinoma after treatment, of which 4 cases were assigned Gleason score: ≥3+4. In cases with residual adenocarcinoma, 8 cases (100%) showed nuclear enlargement, 5 cases (63%), cytoplasmic vacuolization, and 1 case (13%) showed nuclear pyknosis; otherwise, no discernible effects of treatment were seen. Morphological alterations included a spectrum of changes ranging from extensive coagulative stromal necrosis secondary to thermal injury to atrophic changes in benign prostatic tissue after HIFU treatment. Our findings also support the hypothesis that HIFU failure results from inadequate targeting rather than failure within a treated zone.

A Pilot Study of Dynamic 18F-DCFPyL PET/CT Imaging of Prostate Adenocarcinoma in High-Risk Primary Prostate Cancer Patients.

The primary aim of this study was to investigate the pharmacokinetics of 18F-DCFPyL, an 18F-labeled PSMA-based ligand, and to explore the utility of early time point positron emission tomography (PET) imaging extracted from PET data to distinguish malignant primary prostate from benign prostate tissue. Ten consecutive patients with biopsy-proven high-risk prostate cancer underwent a dynamic 18F-DCFPyL PET/CT scan of the pelvis for the first 45 min post-injection (p.i.) followed by a static PET/CT at 2 h p.i. 18F-DCFPyL uptake values and kinetics were compared between benign prostate tissue and prostate cancer, including quantitative pharmacokinetic PET parameters extracted from 18F-DCFPyL time activity curves generated from dynamic data using a two-tissue compartment model and Patlak plots. 18F-DCFPyL uptake values were significantly higher in primary prostate tumors than those in benign prostatic hyperplasia (BPH) and normal prostate tissue at 5 min, 30 min, and 120 min p.i. (P = 0.0002), when examining both SUVmax and SUVmean values. The two-tissue compartment model found an overall influx value (Ki) of 0.063 in primary prostate cancer, demonstrating a Ki over 15-fold higher in malignant prostate tissue compared with BPH (Ki = 0.004) and normal prostate tissue (Ki = 0.005) (P = 0.0001). High-risk primary prostate cancer is readily identified on dynamic and static, delayed, 18F-DCFPyL PET images. The tumor-to-background ratio increases over time, with optimal 18F-DCFPyL PET/CT imaging at 120 min p.i. for evaluation of prostate cancer, but not necessarily ideal for clinical application. Primary prostate cancer demonstrates different uptake kinetics in comparison to BPH and normal prostate tissue. The 15-fold difference in Ki between prostate cancer and non-cancer (BPH and normal) tissues translates to an ability to distinguish prostate cancer from normal tissue at time points as early as 5 to 10 min p.i.

Identification of prostate cancer using multiparametric MR imaging characteristics of prostate tissues referenced to whole mount histopathology

In this study, the objective was to characterize the MR signatures of the various benign prostate tissues and to differentiate them from cancer. Data was from seventy prostate cancer patients who underwent multiparametric MRI (mpMRI) and subsequent prostatectomy. The scans included T2-weighted imaging (T2W), diffusion weighted imaging, dynamic contrast-enhanced MRI (DCE MRI), and MR spectroscopic imaging. Histopathology tissue information was translated to MRI images. The mpMRI parameters were characterized separately per zone and by tissue type. The tissues were ordered according to trends in tissue parameter means. The peripheral zone tissue order was cystic atrophy, high grade prostatic intraepithelial neoplasia (HGPIN), normal, atrophy, inflammation, and cancer. Decreasing values for tissue order were exhibited by ADC (1.8 10−3 mm2/s to 1.2 10−3 mm2/s) and T2W intensity (3447 to 2576). Increasing values occurred for DCE MRI peak (143% to 157%), DCE MRI slope (101%/min to 169%/min), fractional anisotropy (FA) (0.16 to 0.19), choline (7.2 to 12.2), and choline / citrate (0.3 to 0.9). The transition zone tissue order was cystic atrophy, mixed benign prostatic hyperplasia (BPH), normal, atrophy, inflammation, stroma, anterior fibromuscular stroma, and cancer. Decreasing values occurred for ADC (1.6 10−3 mm2/s to 1.1 10−3 mm2/s) and T2W intensity (2863 to 2001). Increasing values occurred for DCE MRI peak (143% to 150%), DCE MRI slope (101%/min to 137%/min), FA (0.18 to 0.25), choline (7.9 to 11.7), and choline / citrate (0.3 to 0.7). Logistic regression was used to create parameter model fits to differentiate cancer from benign prostate tissues. The fits achieved AUCs ≥0.91. This study quantified the mpMRI characteristics of benign prostate tissues and demonstrated the capability of mpMRI to discriminate among benign as well as cancer tissues, potentially aiding future discrimination of cancer from benign confounders.

Characteristics of α2,3-sialyl N-glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level.

BackgroundThe presence of glycosylated isoforms of prostate‐specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3‐sialylated prostate‐specific antigen (S23PSA) by tissue‐based sialylation‐related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA.MethodsTissue‐based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI‐RADS) scores in 98 men prospectively enrolled in a single‐center MRI‐targeted biopsy (MRI–TBx) cohort. The primary outcome was the PC‐diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI‐RADS.ResultsS23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI‐RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI‐RADS + DRE + tPSA was superior to DRE + tPSA+PI‐RADS with avoidance rate of MRI–TBx (13% vs. 1%) at 30% risk threshold.ConclusionsThe diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.

The association of prostatic lipids with progression, racial disparity and discovery of biomarkers in prostate cancer

BackgroundIt remains under-investigated whether prostatic lipid profiles are associated with pathogenesis, progression, racial disparity, and discovery of biomarkers in prostate cancer (PCa). MethodsThe electrospray ionization-tandem mass spectrometry was applied to quantitate prostatic lipids in human and mouse PCa and non-cancer prostatic tissues. Biostatistics and bioinformatics were used to compare the concentrations of prostatic lipids at levels of total lipid, group, class and individual species between PCa and benign prostatic tissues, between races, and among pathological conditions of PCa. ResultsProstatic concentrations of total lipids as well as neutral lipids were significantly higher in PCa than in benign prostatic tissues in all population and Caucasian American population, but not in African American population. The prostatic phospholipid were not statistically different between PCa and benign prostatic tissues in all study populations. Cholesteryl ester is the only lipid class significantly higher in PCa than in benign prostatic tissues in all study populations. A panel of prostatic lipid parameters in each study population was identified as diagnostic and prognostic biomarkers with >60% of sensitivity, specificity and accuracy simultaneously. Lipid profiling on mouse prostatic tissues further confirmed correlation of prostatic lipid profiles to the pathogenesis and progression of PCa. In addition, a few prostatic lipids in mouse can serve as prognostic biomarkers in differentiation of indolent from aggressive PCa. ConclusionThe prostatic lipids are widely associated with the pathogenesis, progression and racial disparity of PCa. A panel of prostatic lipids can serve as diagnostic, prognostic and race-specific biomarkers for PCa.

MP05-06 DIAGNOSTIC ACCURACY OF ADC VALUE ON BIPARAMETRIC MRI FOR DETECTING CLINICALLY SIGNIFICANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Detection & Screening I (MP05)1 Sep 2021MP05-06 DIAGNOSTIC ACCURACY OF ADC VALUE ON BIPARAMETRIC MRI FOR DETECTING CLINICALLY SIGNIFICANT PROSTATE CANCER Jih Hoon Park, Ja Yoon Ku, and Hong Koo Ha Jih Hoon ParkJih Hoon Park More articles by this author , Ja Yoon KuJa Yoon Ku More articles by this author , and Hong Koo HaHong Koo Ha More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001972.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PI-RADS v2 is helpful for the detection of clinically significant prostate cancer (CS-PCa), but does not provide quantitative information. We conducted this study to evaluate the diagnostic accuracy of apparent diffusion coefficient (ADC) value for detecting CS-PCa with TRUS-MR fusion biopsy using 3T biparametric MRI (bpMRI). METHODS: We enrolled 310 patients with elevated PSA level over 4 ng/mL who underwent bpMRI followed by TRUS-MR fusion biopsy of prostate between June 2016 and June 2019. Patients underwent MRI examination on Achieva 3.0T TX MRI Scanner from Philips. The suspicious lesions were indicated by experienced radiologists according to PI-RADS v2, marked as a region-of-interest (ROI) and targeted by TRUS-MR fusion biopsy. ADC values were calculated for a pair of b values: 50 and 1400 s/mm2. ADC values of ROIs were recorded by averaging the values measured at least three times each by two urologists. The size of ROIs was chosen to be as large as possible and with minimal contamination from normal tissue. CS-PCa was defined as ISUP grade of 2 or greater. Lower grade (LG) PCa was defined as ISUP grade 1 or 2, and higher grade (HG) as ISUP grade over 2. RESULTS: Of the 502 lesions indicated and biopsied, 348 (69.3%) were on peripheral zone (PZ) and 154 (30.7%) on transitional zone (TZ). In PZ, 101 (29.0%) lesions were diagnosed with PCa, including 73 (21.0%) with CS-PCa, and in TZ, 39 (25.3%) and 21 (13.6%) were detected with PCa and CS-PCa, respectively. Receiver operating characteristic (ROC) curve analyses showed larger area under curve (AUC) for ADC value compared to PI-RADS (0.902 vs 0.827) for detecting CS-PCa in PZ, but not in TZ (0.797 vs 0.786). According to DeLong test there was a statistically significant better AUC for ADC value on ROC curve analysis compared to PI-RADS in PZ (p=0.0095), but not in TZ (p=0.8496). Mean ADC value (x10-3 mm2/s) of the lesions diagnosed with benign prostatic tissues was 0.929 (95% CI 0.906-0.953), and was different statistically significant with that of LG PCa tissues (mean=0.643, 95% CI 0.591-0.695, p<0.001) and that of HG PCa tissue (mean=0.576, 95% CI 0.540-0.610, p<0.001). The difference between LG and HG PCa tissues was statistically significant (p=0.034). CONCLUSIONS: Predictive role of ADC value on biparametric MRI before TRUS-MR fusion biopsy is better than PI-RADS v2 in detection of CS-PCa. Source of Funding: No source of funding © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e79-e80 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jih Hoon Park More articles by this author Ja Yoon Ku More articles by this author Hong Koo Ha More articles by this author Expand All Advertisement Loading ...

MP01-08 REZŪM WATER VAPOR THERAPY FOR LARGE VOLUME (≥80 ML) BENIGN PROSTATIC ENLARGEMENT: LARGE, MULTI-CENTER COHORT

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology I (MP01)1 Sep 2021MP01-08 REZŪM WATER VAPOR THERAPY FOR LARGE VOLUME (≥80 ML) BENIGN PROSTATIC ENLARGEMENT: LARGE, MULTI-CENTER COHORT Dean Elterman, Naeem Bhojani, Bilal Chughtai, and Kevin C. Zorn Dean EltermanDean Elterman More articles by this author , Naeem BhojaniNaeem Bhojani More articles by this author , Bilal ChughtaiBilal Chughtai More articles by this author , and Kevin C. ZornKevin C. Zorn More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001962.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Open or laser prostatectomy are the standard treatments for benign prostatic hyperplasia (BPH) of large volume prostates ≥80 mL. Rezūm is a minimally invasive procedure to ablate benign prostatic tissue. Herein, we report the prospective, multi-center results of the largest cohort of prostates ≥80 mL treated with Rezum. METHODS: A prospective registry was established for Rezūm therapy in Canada (2019) at two high-volume centers. All patients had baseline medical and BPH history documented along with uroflowmetry (Qmax and PVR), and validated questionnaires (IPSS, IPSS QoL, BPHII, IIEF-15, MSHQ-EjD function and bother). RESULTS: 83 patients (mean age 68.7 years) with prostate size ≥80 ml were treated with Rezūm from April 2019 to Dec 2020. The average prostate volume was 104.6 ml (range 80-160 ml) and 65% had a median lobe. 21 patients had prior episode of urinary retention. Mean number of injections was 13.6 (range 8-28). Mean duration of procedure was 5.9 minutes (range 2.5-14). Mean duration of post-procedure catheterization was 11.8 days. IPSS reduced from a baseline score of 20.9 by 24.3% (15.8), 56.7% (9), 59.1% (8.4) at 1, 3, 12 months respectively. IPSS QoL score improved from a baseline of 4.2 to 1.8 (-56%) at 3 months and 1.4 (-70%) at 12 months. Qmax improves from a baseline of 9.2 ml/s up to 14.3 ml/s (55%) at 3 months. BPHII improved from a baseline of 6.4 to 2.8 (-57%) at 3 months and 1.8 (-71%) at 12 months. IIEF showed no significant change from 52 at baseline to 57 at 12 months. Similarly, no changes in MSHQ function (10.3 to 10.1 at 12 months) or bother (1.4 to 1.3 at 12 months). No Clavien-Dindo events ≥ grade III occurred. CONCLUSIONS: Rezum therapy is safe, effective, quick, out-patient procedure in prostate glands ≥80 ml with similar outcomes to prostates <80 mL. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e3-e3 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dean Elterman More articles by this author Naeem Bhojani More articles by this author Bilal Chughtai More articles by this author Kevin C. Zorn More articles by this author Expand All Advertisement Loading ...

Prevalence of Human Polyomavirus BK Virus in Prostate Cancer Patients and Benign Prostatic Hyperplasia: A Cross-sectional Study on Prostate Patients Referred to Imam Khomeini Hospital in Ahvaz Between 2015 and 2017

Background: Human polyomavirus BK virus (BKV) belongs to the Polyomaviridae family and seems to be a drastic virus in prostate cancer (PCa) etiology. BK virus induces oncogenesis via the expression of large tumor antigen (LTAg) and small tumor antigen (stAg). Also, BKV infection seems to play an essential role in prostate cancer development. Objectives: In this study was aimed to study the prevalence of BKV in benign and cancerous prostate tissues. Methods: In this study, 100 formalin-fixed paraffin-embedded tissues of PCa specimens and benign prostatic hyperplasia (BPH) were collected. The DNA was extracted from tissue samples, and the BKV DNA was investigated using a semi-nested polymerase chain reaction (PCR). The MEGA 6.0 software was used for phylogenetic analysis to assemble the viral genome. A phylogenetic tree was constructed by neighbor-joining analysis with 1,000 replicates of the bootstrap resampling test. Results: The BKV DNA was found in 66% (33/50) of patients with PCa and 36% (18/50) of patients with benign prostatic hyperplasia (BPH) (P = 0.003). The frequency of BKV DNA in different classes of Gleason score (5 - 10) was not significant (0.094). The distribution of BKV DNA among different age groups was not significant (P = 0.086). Conclusions: High frequency of BKV infection was detected in patients with PCa compared to patients with BPH (P = 0.003), and the coexistence of BKV DNA was confirmed in 51% (51/100) of tissue samples, which were confirmed to be subtype 1 of BKV infection.