Adult Prostate Research Articles

Differential Protein-Coding Gene Expression Profile in Patients with Prostate Cancer

Background: Prostate cancer is the second most common neoplasm in men, with projections estimating over one million new cases by 2045. Differentially expressed genes can significantly enhance the diagnosis, treatment, monitoring, and prognosis of this disease. Purpose: to systematically review and analyze validated differentially expressed mRNAs in prostate cancer patients to propose a robust molecular profile for clinical diagnostics. Methods: A systematic review was conducted following PRISMA guidelines, searching literature databases for mRNAs with validated differential expression in adult prostate cancer patients. Identified mRNAs were analyzed using STRING, Cytoscape, and DrugBank to explore protein–protein interactions and potential drug targets. Results: A total of 5003 participants from Europe, Asia, America, and Oceania were included, and 144 mRNAs (p < 0.05) were reported across 75 primary articles, predominantly validated using RT-qPCR with tissue samples. Among these, at least 36 mRNAs were identified as targets for cancer-related drugs. Enrichment analysis revealed the top pathways were associated with cancer, including specific prostate cancer terms. Key nodes emerged as hubs in the protein–protein interaction network. Conclusion: Based on our comprehensive in silico analysis of validated differentially expressed mRNAs, we propose a molecular profile of twenty-five mRNAs with significant potential for clinical diagnosis of prostate cancer. These findings offer a valuable foundation for developing precision oncology strategies to improve patient outcomes.

ASO Visual Abstract: Adult Prostate Sarcoma: Demographics, Treatment Patterns, and Survival

ASO Visual Abstract: Adult Prostate Sarcoma: Demographics, Treatment Patterns, and Survival

Combined developmental exposure to estrogenic endocrine disruptor and nutritional imbalance induces long term adult prostate inflammation through inflammasome activation

Increasing number of studies suggested that environmental deleterious impacts (such as estrogen-like endocrine disruptors, EDCs, unhealthy diet) during early human development affect the risk of developing non-communicable diseases including prostate cancer (PCa) later in life. To test if the combination of EDCs and unhealthy induces adult prostate lesions, we developed an experimental model of adult male Sprague Dawley rats exposed during gestation (from day 7) to weaning to high fat diet (HFD 60 % fat), or to a xenoestrogen (estradiol benzoate, EB, 2.5 µg/d) from post-natal days 1–5, or to a combination of both. EB and EB+HFD exposures induced decreased prostate weight in adult rats along with inflammatory status. A white blood cell infiltrate was observed after EB exposure and more dramatic lesions were observed with the combined exposure, along with a gland destruction. The lesions, following EB or EB+HFD exposure, are associated with elevated mRNA levels for TNFa, IL6 and CCL2/MCP1 pro-inflammatory cytokines while the levels of the anti-inflammatory IL10 cytokine remained unchanged. This activation of NLRP3 and elevated levels of CASP1 were observed following EB or EB+HFD exposures associated with elevated mRNA levels for IL1b, substrates for the NLRP3 complex. HFD exposure alone has mild if not pro-inflammatory effects in adult prostate. In conclusion, we showed that developmental combined exposure to EB and HFD programmed prostate inflammatory lesions in adult prostate. Since proliferative inflammatory atrophy and chronic inflammation of prostate may drive cell to become cancer cells, our model might be useful for study onset of PCa.

Adult Prostate Sarcoma: Demographics, Treatment Patterns, and Survival

BackgroundThis study aimed to examine clinicopathologic characteristics, treatment patterns, and survival rates in a contemporary population-based cohort of adult prostate sarcoma patients.MethodsIn the Surveillance, Epidemiology, and End Results database (2004–2020), adult patients with prostate sarcoma were identified. Descriptive statistics, Kaplan–Meier analyses, smoothed cumulative incidence plots, and Cox regression models were used.ResultsOf 125 patients, 45 (36%) harbored leiomyosarcoma, 17 (14%) had rhabdomyosarcoma, 15 (12%) had stromal sarcoma, 17 (14%) had sarcoma not otherwise specified (NOS), and 31 (25%) had other sarcoma subtypes. Metastatic stage was most common in the rhabdomyosarcoma patients (44%) and least common in the leiomyosarcoma (21%) and stromal sarcoma (20%) patients. Most of the rhabdomyosarcoma patients received the combination of systemic and radiation therapy with (24%) or without radical surgery (35%), whereas most of the leiomyosarcoma and stromal sarcoma patients underwent radical surgery with (22 and 13%) or without (22 and 47%) radiation. In the overall population, the median overall survival was 27 months. The 5-years overall versus cancer-specific versus other-cause mortality rates were respectively 71 versus 58 versus 13%. In the multivariable Cox regression models, the highest overall mortality was exhibited by the patients with metastatic disease (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.55–5.31; p < 0.001) or unknown disease stage (HR 2.94; 95% CI 2.20–7.21; p = 0.019). Conversely, of all the histologic subtypes, only stromal sarcoma distinguished itself by lower overall mortality (HR 0.41; 95% CI 0.18–0.96; p = 0.039).ConclusionsFour major histologic subtypes were identified. Among most adult sarcoma patients, treatment patterns vary according to histology, from multimodal therapy to radical prostatectomy alone. These treatment differences reflect equally important heterogeneity in survival patterns.

Prostate Cancer Related Sexual Dysfunction and Barriers to Help Seeking: A Scoping Review.

Despite available support, sexuality needs are the most frequently reported unmet need among men with prostate cancer, which may be due to low help-seeking rates. Using the Ecological Systems Framework as a theoretical foundation, we conducted a scoping review of the available literature to understand what factors impact help-seeking behaviour for sexual issues after prostate cancer treatment among men who had received treatment. Following PRISMA guidelines, a systematic search on Medline, PsychInfo, Embase, Emcare, and Scopus was conducted to identify studies of adult prostate cancer patients post-treatment, which reported barriers and/or facilitators to help-seeking for sexual health issues. Quality appraisals were conducted using Joanna Briggs Institute appraisal tools, and results were qualitatively synthesised. Of the 3870 unique results, only 30 studies met inclusion criteria. In general, studies were considered moderate to good quality, though only six used standardised measures to assess help-seeking behaviour. Barriers and facilitators for sexual help-seeking were identified across all five levels of the Ecological Systems Framework, including age, treatment type, and previous help seeking experience (individual level), healthcare professional communication and partner support (microsystem), financial cost and accessibility of support (meso/exosystem), and finally embarrassment, masculinity, cultural norms, and sexuality minority (macrosystem). Addressing commonly reported barriers (and inversely, enhancing facilitators) to help-seeking for sexual issues is essential to ensure patients are appropriately supported. Based on our results, we recommend healthcare professionals include sexual wellbeing discussions as standard care for all prostate cancer patients, regardless of treatment received, age, sexual orientation, and partnership status/involvement.

Rhabdomyosarcoma of prostate presenting as prostatic abscess in young adult – Rare presentation of a rare disease

Abstract Rhabdomyosarcoma (RMS) of the prostate in adults is a rare but highly malignant tumor and often metastatic at diagnosis. RMS of the prostate in adults has been reported in isolated case reports in the literature. Timely diagnosis and multimodal treatment give the best survival chance to the patient. The varied presentation of RMS of the prostate in adults mimicking multiple other pathologies of the prostate and lack of pathognomic radiological findings makes its diagnosis difficult and delays in treatment. Transrectal biopsy of the prostate with immunohistochemistry panel at histopathological examination confirms the diagnosis. A 27-year-old man diagnosed as prostatic abscess and treated with antibiotics was referred to our center. Adequate suspicion of malignancy with proper evaluation and biopsy leads to correct diagnosis of RMS of the prostate. Multimodality treatment was initiated as the disease was not metastatic at diagnosis.

Abstract 7077: The oncogenic transcription factor ERG has distinct roles and signaling in different prostate cancer cell types

Abstract ERG is the most common oncogene in prostate cancer, as it is aberrantly expressed in about 50% of cases due to the TMPRSS2/ERG gene rearrangement. ERG is not normally expressed in the adult prostate. The normal function of ERG is confined to hematopoietic stem cells and blood vessels. Aberrant expression of ERG in prostate epithelial cells is oncogenic when combined with mutations that activate the PI3K/AKT signaling pathway. The RAS/MAPK pathway can also regulate ERG function through direct phosphorylation of ERG by ERK. The function of these regulatory events and how they can be exploited to develop therapy for ERG-positive prostate cancer remains unclear. Here we find that ERG expression in prostate epithelial cells with low PI3K/AKT pathway activity drives epithelial to mesenchymal transition and stemness properties. This function requires ERG phosphorylation via a positive feedback loop with the TLR4 signaling pathway, and can be repressed by a TLR4 inhibitor. However, activation of the PI3K/AKT pathway rearranges the ERG cistrome and alters ERG function, where ERG now promotes luminal epithelial differentiation. In the presence of activated AKT, new ERG targets include genes involved in vascular development and ERG phosphorylation is regulated through a positive feedback loop with the VEGF signaling pathway. Despite these differences in cellular differentiation, we find that ERG can promote stemness and tumorigenesis in both AKT-high and AKT-low cellular backgrounds. ERG functions in prostate epithelial cells appear to mirror ERG functions in hematopoietic stem cells and blood vessels. These findings suggest strategies of combinatorial inhibition of ERG function through signaling pathway inhibition. Citation Format: Saranya Rajendran, Peter C. Hollenhorst. The oncogenic transcription factor ERG has distinct roles and signaling in different prostate cancer cell types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7077.

Abstract 5323: Inflammation drives lineage plasticity and a club cell-like phenotype in prostate epithelial cells

Abstract Background: Club cells are a type of bronchiolar epithelial cell that serve a protective and antimicrobial function in the lung. An epithelial cell population in adult human prostates was recently identified as sharing a similar transcriptomic profile and morphology to lung club cells. Club-like epithelial cells were identified in the prostatic urethra, collecting ducts, and rarely in the peripheral zone of normal organ donor prostates. However, we recently reported that cells expressing club cell markers (CP, LTF, MMP7, PIGR, SCGB1A1) are present in the peripheral zone of radical prostatectomy specimens. Here, expression of club cell markers was restricted to luminal epithelial cells in an inflammation-associated lesion termed proliferative inflammatory atrophy (PIA). We also demonstrated that these club-like cells within PIA express the same markers as intermediate cells, a proposed prostate cancer progenitor cell. We now aim to identify exogenous factors that drive the club cell phenotype in vitro. Our ultimate goal is to understand how club cell gene expression affects the oncogenic and metastatic potential of prostate epithelial cells. Methods: We characterized the expression of club cell genes in prostate cell lines (LNCaP, PREC, and PREC-AR-Myc) following exposure to inflammatory stimuli (TNFα, hydrogen peroxide, uropathogenic Escherichia coli) in vitro. We performed quantitative reverse transcription PCR (RT-qPCR) to measure expression of club cell markers (LTF, MMP7, PIGR) and intermediate cell markers (AR, NKX3.1, SMOX). Additionally, we used chromogenic RNA in situ hybridization (RISH) to visualize LTF, MMP7, and PIGR expression following exposure to inflammatory stimuli. Results: We report that TNFα exposure in vitro increased expression of club cell genes (LTF, MMP7, PIGR). Surprisingly, TNFα exposure induced LTF expression in LNCaP cells, despite prior findings that LTF is silenced by CpG island hypermethylation in prostate cancer and in LNCaP cells. This finding was confirmed by both RT-qPCR and RISH. Additionally, we found that TNFα exposure altered intermediate cell markers (AR, NKX3.1, SMOX) expression consistent with the previously reported gene expression pattern of luminal epithelial cells in PIA. Conclusions: Overall, our results suggest that TNFα-mediated signaling drives the expression of club cell markers associated with lineage plasticity. Our next step will be to analyze inflammation-driven alterations to methylation and chromatin accessibility around loci associated with club cell genes, proton-oncogenes, and tumor suppressor genes. Citation Format: Megan Hess, Hanbing Song, Jessica Hicks, Luke Mummert, Angelo De Marzo, Franklin W. Huang, Karen Sfanos. Inflammation drives lineage plasticity and a club cell-like phenotype in prostate epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5323.

Spatial transcriptomics identifies candidate stromal drivers of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the nodular proliferation of the prostate transition zone in older men, leading to urinary storage and voiding problems that can be recalcitrant to therapy. Decades ago, John McNeal proposed that BPH originates with the "reawakening" of embryonic inductive activity by adult prostate stroma, which spurs new ductal proliferation and branching morphogenesis. Here, by laser microdissection and transcriptional profiling of the BPH stroma adjacent to hyperplastic branching ducts, we identified secreted factors likely mediating stromal induction of prostate glandular epithelium and coinciding processes. The top stromal factors were insulin-like growth factor 1 (IGF1) and CXC chemokine ligand 13 (CXCL13), which we verified by RNA in situ hybridization to be coexpressed in BPH fibroblasts, along with their cognate receptors (IGF1R and CXCR5) on adjacent epithelium. In contrast, IGF1 but not CXCL13 was expressed in human embryonic prostate stroma. Finally, we demonstrated that IGF1 is necessary for the generation of BPH-1 cell spheroids and patient-derived BPH cell organoids in 3D culture. Our findings partially support historic speculations on the etiology of BPH and provide what we believe to be new molecular targets for rational therapies directed against the underlying processes driving BPH.

MED19 encodes two unique protein isoforms that confer prostate cancer growth under low androgen through distinct gene expression programs

MED19, a component of the mediator complex and a co-regulator of the androgen receptor (AR), is pivotal in prostate cancer cell proliferation. MED19 has two isoforms: a full-length “canonical” and a shorter “alternative” variant. Specific antibodies were developed to investigate these isoforms. Both exhibit similar expression in normal prostate development and adult prostate tissue, but the canonical isoform is elevated in prostate adenocarcinomas. Overexpression of canonical MED19 in LNCaP cells promotes growth under conditions of androgen deprivation in vitro and in vivo, mirroring earlier findings with alternative MED19-overexpressing LNCaP cells. Interestingly, alternative MED19 cells displayed strong colony formation in clonogenic assays under conditions of androgen deprivation, while canonical MED19 cells did not, suggesting distinct functional roles. These isoforms also modulated gene expression differently. Canonical MED19 triggered genes related to extracellular matrix remodeling while suppressing those involved in androgen-inactivating glucuronidation. In contrast, alternative MED19 elevated genes tied to cell movement and reduced those associated with cell adhesion and differentiation. The ratio of MED19 isoform expression in prostate cancers shifts with the disease stage. Early-stage cancers exhibit higher canonical MED19 expression than alternative MED19, consistent with canonical MED19’s ability to promote cell proliferation under androgen deprivation. Conversely, alternative MED19 levels were higher in later-stage metastatic prostate cancer than in canonical MED19, reflecting alternative MED19’s capability to enhance cell migration and autonomous cell growth. Our findings suggest that MED19 isoforms play unique roles in prostate cancer progression and highlights MED19 as a potential therapeutic target for both early and late-stage prostate cancer.

1776P Body composition in adult life and prostate cancer (PCa) incidence and mortality: The PROCA-life study

1776P Body composition in adult life and prostate cancer (PCa) incidence and mortality: The PROCA-life study

Cancer Statistics in Pakistan From 1994 to 2021: Data From Cancer Registry.

Pakistan has been systematically collecting cancer data since 1994 through cancer registries. This article presents a comprehensive analysis of cancer statistics in Pakistan from 1994 to 2021, including incidence and patterns. The total number of patients with malignant neoplasm was 111,941, and the number of patients registered was 109,863. Most patients were from Punjab (67.6%) and Khyber Pakhtunkhwa (20.2%). Breast cancer (22.2%), colorectum cancer (5.6%), leukemia (5.3%), lip and oral cavity cancer, and non-Hodgkin lymphoma (5.1%) were the top five prevalent cancers in all age groups and sexes. Breast (24.2%), colorectum (6.2%), lip and oral cavity (5.8%), non-Hodgkin lymphoma (4.4%), and prostate cancers (4.0%) were most common in adults in both sexes. In both sexes, the most common cancers among children were Hodgkin lymphoma (20.1%), acute lymphoblastic leukemia (19.8%), non-Hodgkin lymphoma (11.6%), osteosarcoma (7.0%), and retinoblastoma (6.2%). Breast (45.9%), ovary and uterine adnexa (4.9%), lip and oral cavity (4.2%), cervix uteri (4.0%), and colorectum cancers (3.9%) were most common in adult females. In adult males, colorectum cancer (8.7%), prostate cancer (8.5%), lip and oral cavity cancer (7.6%), non-Hodgkin lymphoma (6.4%), and liver and intrahepatic bile duct cancers were the top five most common malignancies. It has been found that breast cancer, colorectum cancer, prostate cancer, leukemia, and bone cancer rates are among the highest in Pakistan. This information may be useful in assessing the effectiveness of future intervention strategies.

Club-like cells in proliferative inflammatory atrophy of the prostate.

Club cells are a type of bronchiolar epithelial cell that serve a protective role in the lung and regenerate damaged lung epithelium. Single-cell RNA sequencing (scRNA-seq) of young adult human prostate and urethra identified cell populations in the prostatic urethra and collecting ducts similar in morphology and transcriptomic profile to lung club cells. We further identified club cell-like epithelial cells by scRNA-seq of prostate peripheral zone tissues. Here, we aimed to identify and spatially localize club cells in situ in the prostate, including in the peripheral zone. We performed chromogenic RNA in situ hybridization for five club cell markers (CP, LTF, MMP7, PIGR, SCGB1A1) in a series of (1) nondiseased organ donor prostate and (2) radical prostatectomy specimens from individuals with prostate cancer. We report that expression of club cell genes in the peripheral zone is associated with inflammation and limited to luminal epithelial cells classified as intermediate cells in proliferative inflammatory atrophy (PIA). Club-like cells were enriched in radical prostatectomy specimens compared to nondiseased prostates and associated with high-grade prostate cancer. We previously reported that luminal epithelial cells in PIA can rarely harbor oncogenic TMPRSS2:ERG (ERG+) gene fusions, and we now demonstrate that club cells are present in association with ERG+ PIA that is transitioning to early adenocarcinoma. Finally, prostate epithelial organoids derived from prostatectomy specimens demonstrate that club-like epithelial cells can be established in organoids and are sensitive to anti-androgen-directed treatment in vitro in terms of decreased androgen signaling gene expression signatures compared to basal or hillock cells. Overall, our study identifies a population of club-like cells in PIA and proposes that these cells play an analogous role to that of club cells in bronchiolar epithelium. Our results further suggest that inflammation drives lineage plasticity in the human prostate and that club cells in PIA may be prone to oncogenic transformation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Characterization of olfactomedin 4+ cells in prostate and urethral-tube epithelium during murine postnatal development and in adult mice

Olfactomedin4 (Olfm4) is expressed in normal mouse prostate. However, Olfm4+ cells in the murine prostate have not been well characterized. In this study, we generated an Olfm4eGFP reporter mouse line with C57BL/6 mice and investigated the distribution of Olfm4/eGFP-expressing cells during postnatal development from P1, P7, P14, P20, P42, P56 to adult male mouse prostate and urethral tube. We observed Olfm4/eGFP expression in urogenital and prostatic epithelial cells during early postnatal development, which persisted into adulthood in urethral-tube and anterior-prostate (AP) epithelium. We found Olfm4+ cells are E-cadherin+/CD44+/Foxa1+ and some of subpopulation are Ck8+/Ck5+/Sca-1-/Ck4-/Syn- in the adult mouse AP epithelium. Functional studies of single-cell preparations of Olfm4/eGFP-expressing cells isolated from adult Olfm4eGFP mouse prostate demonstrated that Olfm4+ cells can grow and form colonies, spheres, or organoids in culture. Bioinformatic analysis of Olfm4+ cells using single-cell RNA sequencing meta data in adult mouse urethra (GSE145865) identified upregulation of genes related to cell and tissue migration and development, as well as upregulation of xenobiotic metabolism signaling pathways. In conclusion, Olfm4eGFP mouse is a novel model to further study Olfm4’s biological functions and Olfm4+ cells may contribute importantly to cellular processes supporting development and homeostasis of the epithelium in murine prostate and urethral tube.

Abstract B005: The oncogenic transcription factor ERG has distinct roles and signaling regulation in different prostate cancer cell types

Abstract Background: ERG is the most common oncogene in prostate cancer, as it is aberrantly expressed in about 50% of cases due to the TMPRSS2/ERG gene rearrangement. ERG is not normally expressed in the adult prostate. The normal function of ERG is confined to hematopoietic stem cells and blood vessels. Aberrant expression of ERG in prostate epithelial cells is oncogenic when combined with mutations that activate the PI3K/AKT signaling pathway. The RAS/MAPK pathway can also regulate ERG function through direct phosphorylation of ERG by ERK. The function of these regulatory events and how they can be exploited to develop therapy for ERG-positive prostate cancer remains unclear. Results: ERG expression in prostate basal epithelial cells drives epithelial to mesenchymal transition and stemness properties. This function requires ERG phosphorylation via a positive feedback loop with the TLR4 signaling pathway, and can be repressed by a TLR4 inhibitor. Activation of the PI3K/AKT pathway rearranges the ERG cistrome and alters ERG function, where ERG now promotes luminal epithelial differentiation. In the presence of activated AKT, new ERG targets include genes involved in vascular development and ERG phosphorylation is regulated through a positive feedback loop with the VEGF signaling pathway. Conclusions: ERG function in basal and luminal prostate epithelial cells appear to mirror ERG functions in hematopoietic stem cells and blood vessels, respectively. These findings suggest strategies of combinatorial inhibition of ERG function in both cell types. Citation Format: Peter C. Hollenhorst, Saranya Rajendran, Travis J. Jerde. The oncogenic transcription factor ERG has distinct roles and signaling regulation in different prostate cancer cell types [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B005.

Abstract PR009: Basal cell lineage plasticity in prostate homeostasis, repair and tumor initiation

Abstract Androgen deprivation is the paradigm of prostate cancer treatment. It is often linked to the loss of luminal cells, but the basal cell fates under androgen deprivation, prostatitis and cancer initiation remain unclear. Using a genetic proliferation tracer (ProTracer) system, we found that adult prostate basal cells also had extensive cell loss and proliferation during androgen-mediated prostate regression and regeneration. A rare basal population that expresses luminal cell genes (termed Basal-B) and a large basal population (termed Basal-A) were identified in the mouse prostate by single-cell RNA sequencing. Basal-B cells exhibited greater capacity for organoid formation and luminal cell differentiation in vitro. Basal-A and Basal-B cells were specifically tracked at the same time in vivo using a genetic lineage-tracing system that uses dual recombinases (Cre and Dre). Fate-mapping showed that prostate basal regeneration is not driven by rare Basal-B cells. Clonal analysis showed that Basal-B cells had the better tendency to generate luminal cells under bacteria-induced prostatitis. Moreover, oncogenic transformation of basal cells promoted the Basal-B cell marker gene expression in vivo. This study provides genetic evidence of a bona fide of basal cell lineage plasticity under androgen deprivation, prostatitis and oncogenic transformation contexts. Citation Format: Dong Gao. Basal cell lineage plasticity in prostate homeostasis, repair and tumor initiation [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR009.

The impacts of exposure to bisphenol A in the adult female prostate Meriones unguiculatus

The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-β estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERβ, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate.

PD02-05 SRD5A2 EXPRESSION IS A PREDICTOR OF RESPONSE TO FINASTERIDE IN THE MTOPS TRIAL

You have accessJournal of UrologyCME1 Apr 2023PD02-05 SRD5A2 EXPRESSION IS A PREDICTOR OF RESPONSE TO FINASTERIDE IN THE MTOPS TRIAL Ra'ad Al-Faouri, Christina Sharkey, Zongwei Wang, and Aria F. Olumi Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Christina SharkeyChristina Sharkey More articles by this author , Zongwei WangZongwei Wang More articles by this author , and Aria F. OlumiAria F. Olumi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Medical Therapy Of Prostatic Symptoms (MTOPS) study was a multi-center, randomized, controlled clinical trial conducted between 1995 and 2001 aiming to evaluate the effect of finasteride, doxazosin, or a combination of both drugs on the progression of urinary symptoms in men with benign prostatic hyperplasia (BPH). We have demonstrated that 30% of adult prostates do not express SRD5A2 through epigenetic regulation, enabling us to postulate that expression of SRD5A2 may be related to response to finasteride. Prostate biopsies and clinical data from 82 MTOPS trial participants were obtained to test the correlation between baseline expression of SRD5A2 and the response to medical treatment with finasteride. METHODS: We classified men based on changing their AUA symptom score (AUA SS) into good responders (change of AUASS ≤-12) and poor responders (change of AUASS ≥-2). Using immunoreactive score system (IRS score), we quantified the expression of SRD5A2 in the biopsies. We compared baseline age, demographics, AUA SS, BMI, serum dihydrotestosterone (DHT) between men in the two groups. RESULTS: There was no significant difference in TPV between the two groups. Men in the 5ARI good response group were found to have higher expression of SRD5A2 compared to men in the 5ARI poor response group (p-value <0.007). In addition, there was a statistically significant correlation between the expression of SRD5A2 and the 5-year change in AUASS (Pearson's correlation coefficient: -0.4279, p-value: 0.02). In a multiple linear regression model that adjusted for baseline AUA SS, baseline total prostate volume, baseline serum DHT level, age, and BMI, men with higher expression of SRD5A2 still had better response to finasteride with better improvement of urinary symptoms as reflected by AUA symptoms scores. CONCLUSIONS: The MTOPS study was a significant milestone in the curation BPH medical management. Since expression of SRD5A2 is epigenetically regulated during adulthood, our analysis of the biopsies and clinical data provided from the trial shines a light on the importance of SRD5A2 activity and response to 5-ARI therapy. The level of response to 5-ARI therapy correlated to higher SRD5A2 expression. This may contribute to precision medicine by predicting men that are most likely to benefit from tailored therapy by 5-ARI. Source of Funding: NIH: R01DK124502; X01DK131477 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e70 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ra'ad Al-Faouri More articles by this author Christina Sharkey More articles by this author Zongwei Wang More articles by this author Aria F. Olumi More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate imaging features on magnetic resonance imaging of young patients.

To identify magnetic resonance imaging findings of the prostate in young adults, including symptomatic and asymptomatic patients. The aim of this study is to evaluate the main aspects of prostate imaging in young patients. A total of 102 patients under 40 years of age, who underwent prostate magnetic resonance imaging between January 2016 and January 2019, were included in this study. The patients were divided into two groups: symptomatic for prostatitis (Group 1) and asymptomatic (Group 2). Magnetic resonance imaging scans were anonymized and interpreted by a radiologist blinded for clinical information. The study evaluated peripheral zone signal in T2-weighted sequences, diffusion and apparent diffusion coefficient map; peripheral zone enhancement pattern; seminal vesicles and periprostatic fat. All evaluated criteria did not present statistically significant differences between the two groups. The most common pattern was heterogeneous hyposignal on T2 (57.9% in Group 1 and 57.8% in Group 2; p=0.506), mild diffuse / wedge-shaped areas of hypointensity on apparent diffusion coefficient map (61.4% in Group 1 and 64.4% in Group 2; p=0.931) and early post-contrast enhancement (73.7% in Group 1 and 68.9% in Group 2, p=0719). The magnetic resonance imaging aspect of young patients showed no differences between symptomatic and asymptomatic patients.

Disparities in place of death from prostate cancer revealed by disaggregation of Asian race.

187 Background: Place of death (PoD) is a surrogate determinant of health care inequity in patients with cancer. Aggregation of Asian Americans, a diverse group, may mask significant health disparities in end-of-life care. Methods: De-identified death certificate data were obtained via the National Center for Health Statistics. All adult (&gt; 18 years of age) prostate cancer deaths from 2018 to 2019 were included. Multinomial logistic regression was used to test for differences in place of death associated with sociodemographic variables. Results: From 2018 through 2019, 81,292 adults died from prostate cancer. Overall, most Asians were less likely to die at home (p &lt; 0.05) or nursing facility (p &lt; 0.05) compared to White patients. Significant differences in nursing facility use was noted in disaggregated analysis, with Samoan patients 12.44 times more likely to die in a hospice facility compared to hospital (CI 2.89, 53.6; p &lt; 0.001) and Chinese patients 100 times less likely to die in a hospice facility (CI 0.01, 0.02; p &lt; 0.001) to give two notable examples. Chinese (OR 0.26), Guamanian (OR 0.2), and Vietnamese race (OR 0.05) had the lowest likelihood of dying at home, with odds ratio lower than Black race (OR 0.3) (Table). Conclusions: Increased attention to PoD over recent years has highlighted issues around equity in end-of-life care. Overall, our data underscore important differences among Asian subpopulations and possible barriers to quality end of life care that would otherwise be masked with data aggregation. It is well known that resources are needed to allow death at home or at a nursing facility. Further qualitative work is planned to investigate culture differences contributing to PoD differences for patients with cancer through the lens of the social determinants of health.