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Annals of Medicine 2023Tumour classifications play a pivotal role in prostate cancer (PCa) management. It can predict the clinical outcomes of PCa as early as the disease is diagnosed and then... (Review)
Review
Tumour classifications play a pivotal role in prostate cancer (PCa) management. It can predict the clinical outcomes of PCa as early as the disease is diagnosed and then guide therapeutic schemes, such as active monitoring, standalone surgical intervention, or surgery supplemented with postoperative adjunctive therapy, thereby circumventing disease exacerbation and excessive treatment. Classifications based on clinicopathological features, such as prostate cancer-specific antigen, Gleason score, and TNM stage, are still the main risk stratification strategies and have played an essential role in standardized clinical decision-making. However, mounting evidence indicates that clinicopathological parameters in isolation fail to adequately capture the heterogeneity exhibited among distinct PCa patients, such as those sharing identical Gleason scores yet experiencing divergent prognoses. As a remedy, molecular classifications have been introduced. Currently, molecular studies have revealed the characteristic genomic alterations, epigenetic modulations, and tumour microenvironment associated with different types of PCa, which provide a chance for urologists to refine the PCa classification. In this context, numerous invaluable molecular classifications have been devised, employing disparate statistical methodologies and algorithmic approaches, encompassing self-organizing map clustering, unsupervised cluster analysis, and multifarious algorithms. Interestingly, the classifier PAM50 was used in a phase-2 multicentre open-label trial, NRG-GU-006, for further validation, which hints at the promise of molecular classification for clinical use. Consequently, this review examines the extant molecular classifications, delineates the prevailing panorama of clinically pertinent molecular signatures, and delves into eight emblematic molecular classifications, dissecting their methodological underpinnings and clinical utility.
Topics: Male; Humans; Prostatic Neoplasms; Prognosis; Prostate-Specific Antigen; Neoplasm Grading; Risk Assessment; Tumor Microenvironment
PubMed: 37939258
DOI: 10.1080/07853890.2023.2279235 -
Hormones & Cancer Apr 2017Activins are members of the TGF-β superfamily and have been linked to prostate cancer. There are four mammalian activin subunits (β, β, β, and β) that dimerize to...
Activins are members of the TGF-β superfamily and have been linked to prostate cancer. There are four mammalian activin subunits (β, β, β, and β) that dimerize to form functional proteins. The role of activin-A (β-β) has been relatively well characterized and has been shown to generally inhibit growth in the prostate. In contrast, little is known about the biological function of the β and β subunits. Previous work indicated activin-C (β-β) to be an antagonist of activin-A. This is important because resistance to activin-A growth inhibition occurs during prostate cancer progression. This paradox is not currently well understood. Hence, we hypothesize that local expression of the activin-β subunit antagonizes activin-A-dependent growth inhibition and represents a key factor contributing to acquired insensitivity to activin-A observed in prostate cancer progression. To test our hypothesis, we characterized the ventral prostate lobes of 9-month-old transgenic mice over-expressing activin-β and examined the expression of activin-β, activin-β, and the activin intracellular signaling factor, Smad-2, in human prostate diseases. Prostate epithelial cell hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN) lesions, alterations in cell proliferation, and reduced Smad-2 nuclear localization were evident in mice over-expressing activin-β. Increased activin-β and -β subunit immunoreactive scores and decreased Smad-2 nuclear localization were also evident in human prostate cancer. This study suggests that over-expression of activin-β is associated with murine and human prostate pathologies. We conclude that the activin-β subunit may have therapeutic and/or diagnostic implications in human prostate disease.
Topics: Animals; Cell Nucleus; Gene Expression Regulation, Neoplastic; Humans; Inhibin-beta Subunits; Male; Mice; Mice, Transgenic; Neoplasm Staging; Neoplasms, Experimental; Prostatic Neoplasms; Signal Transduction; Smad2 Protein; Tissue Array Analysis; Up-Regulation
PubMed: 28116672
DOI: 10.1007/s12672-017-0283-8 -
Asian Pacific Journal of Cancer... 2011Understanding the relationship between ethnicity and free prostate specific antigen (fPSA) could identify the population that should be targeted for intervention and...
Understanding the relationship between ethnicity and free prostate specific antigen (fPSA) could identify the population that should be targeted for intervention and prevention program regarding prostate disease. In this study, we therefore examine the effects of aging and ethnicity on fPSA, measured in serum by chemiluminescent assay (CLIA) method of 351 men visiting Tribhuvan University Teaching Hospital (TUTH) for fPSA test from December to March. Medicinal records abstracts were used to obtain information regarding the ethnicity and age of the cases. Those cases whose age and surname could not be obtained were excluded in our study. The subjects were stratified in four ethnic groups viz; Indo-Nepalese, Tibeto-Nepalese, Indigenous and Other based on the origin. The relationship between age and fPSA level was analysed using bivariate coorelation. The age and the fPSA level of the cases were expressed in Mean ± SEM. The association among different age-group and ethnicity with fPSA were analysed using one way ANOVA. The mean fPSA and mean age of the subjects were 1.74 ± 0.22 and 66.84 ± 0.64 respectively. fPSA level was fairly correlated with the age (r=0.146, p=<0.01). The mean fPSA level (ng/ml) among the four age category (<45, 45-60, 60-75 and >75) were 0.49 ± 0.13, 0.69 ± 0.10, 1.94 ± 0.04 and 2.33 ± 0.43 respectively. The difference in mean fPSA level among four different age-groups was statistically significant (p=0.031). Analysis showed no correlation between the fPSA level and the ethnicity. These data suggest that the fPSA level is associated with the age.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers, Tumor; Early Detection of Cancer; Ethnicity; Humans; Male; Mass Screening; Middle Aged; Nepal; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Neoplasms
PubMed: 22320948
DOI: No ID Found -
Archives of Pathology & Laboratory... Aug 2018- The presence of cribriform glands/ducts in the prostate can pose a diagnostic challenge. Cribriform glands/ducts include a spectrum of lesions, from benign to... (Review)
Review
CONTEXT
- The presence of cribriform glands/ducts in the prostate can pose a diagnostic challenge. Cribriform glands/ducts include a spectrum of lesions, from benign to malignant, with vastly different clinical, prognostic, and treatment implications.
OBJECTIVE
- To highlight the diagnostic features of several entities with a common theme of cribriform architecture. We emphasize the importance of distinguishing among benign entities such as cribriform changes and premalignant to malignant entities such as high-grade prostatic intraepithelial neoplasia, atypical intraductal cribriform proliferation, intraductal carcinoma of the prostate, and invasive adenocarcinoma (acinar and ductal types). The diagnostic criteria, differential diagnosis, and clinical implications of these cribriform lesions are discussed.
DATA SOURCES
- Literature review of pertinent publications in PubMed up to calendar year 2017. Photomicrographs obtained from cases at the University of California at Irvine and authors' collections.
CONCLUSIONS
- Although relatively uncommon compared with small acinar lesions (microacinar carcinoma and small gland carcinoma mimickers), large cribriform lesions are increasingly recognized and have become clinically and pathologically important. The spectrum of cribriform lesions includes benign, premalignant, and malignant lesions, and differentiating them can often be subtle and difficult. Intraductal carcinoma of the prostate in particular is independently associated with worse prognosis, and its presence in isolation should prompt definitive treatment. Patients with atypical intraductal cribriform proliferation, intraductal carcinoma of the prostate, or even focal cribriform pattern of invasive adenocarcinoma in biopsies would not be ideal candidates for active surveillance because of the high risk of adverse pathologic findings associated with these entities.
Topics: Diagnosis, Differential; Humans; Male; Prostate; Prostatic Diseases
PubMed: 30040459
DOI: 10.5858/arpa.2018-0005-RA -
Wiley Interdisciplinary Reviews.... 2013The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals,... (Review)
Review
The prostate is a branched ductal-acinar gland that is part of the male reproductive tract. Prostate development depends upon the integration of steroid hormone signals, paracrine interactions between the stromal and epithelial tissue layers, and the actions of cell autonomous factors. Several genes and signaling pathways are known to be required for one or more steps of prostate development including epithelial budding, duct elongation, branching morphogenesis, and/or cellular differentiation. Recent progress in the field of prostate development has included the application of genome-wide technologies including serial analysis of gene expression, expression profiling microarrays, and other large-scale approaches to identify new genes and pathways that are essential for prostate development. The aggregation of experimental results into online databases by organized multilab projects including the Genitourinary Developmental Molecular Atlas Project has also accelerated the understanding of molecular pathways that function during prostate development and identified links between prostate anatomy and molecular signaling. Rapid progress has also recently been made in understanding the nature and role of candidate stem cells in the developing and adult prostate. This has included the identification of putative prostate stem cell markers, lineage tracing, and organ reconstitution studies. However, several issues regarding their origin, precise nature, and possible role(s) in disease remain unresolved. Nevertheless, several links between prostatic developmental mechanisms and the pathogenesis of prostatic diseases including benign prostatic hyperplasia and prostate cancer have led to recent progress on targeting developmental pathways as therapeutic strategies for these diseases.
Topics: Androgens; Animals; Humans; Male; Mice; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Signal Transduction
PubMed: 23335485
DOI: 10.1002/wsbm.1208 -
International Journal of Molecular... Apr 2023Cardiovascular diseases (CVDs) and complications are often seen in patients with prostate cancer (PCa) and affect their clinical management. Despite acceptable safety... (Review)
Review
Cardiovascular diseases (CVDs) and complications are often seen in patients with prostate cancer (PCa) and affect their clinical management. Despite acceptable safety profiles and patient compliance, androgen deprivation therapy (ADT), the mainstay of PCa treatment and chemotherapy, has increased cardiovascular risks and metabolic syndromes in patients. A growing body of evidence also suggests that patients with pre-existing cardiovascular conditions show an increased incidence of PCa and present with fatal forms of the disease. Therefore, it is possible that a molecular link exists between the two diseases, which has not yet been unraveled. This article provides insight into the connection between PCa and CVDs. In this context, we present our findings linking PCa progression with patients' cardiovascular health by performing a comprehensive gene expression study, gene set enrichment (GSEA) and biological pathway analysis using publicly available data extracted from patients with advanced metastatic PCa. We also discuss the common androgen deprivation strategies and CVDs most frequently reported in PCa patients and present evidence from various clinical trials that suggest that therapy induces CVD in PCa patients.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Cardiovascular Diseases
PubMed: 37108147
DOI: 10.3390/ijms24086984 -
International Braz J Urol : Official... 2008
Topics: Biopsy, Needle; Humans; Male; Prostate; Prostatic Diseases
PubMed: 18986556
DOI: No ID Found -
The Urologic Clinics of North America Aug 2011Research into the role of cholesterol and prostate disease has been ongoing for many years, but our mechanistic and translational understanding is still poor. Recent... (Review)
Review
Research into the role of cholesterol and prostate disease has been ongoing for many years, but our mechanistic and translational understanding is still poor. Recent evidence indicates that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer. This article reviews the literature on the relationship between circulating cholesterol and prostate cancer. The data strongly point to hypercholesterolemia as a risk factor for prostate cancer progression and suggest clinical opportunities for the use of cholesterol-lowering therapies to alter disease course.
Topics: Androgens; Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Pravastatin; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors
PubMed: 21798387
DOI: 10.1016/j.ucl.2011.04.001 -
The Pan African Medical Journal 2013Prostatic parenchymal calculi are common, usually incidental, findings on morphological examinations. They are typically asymptomatic and may be present in association...
Prostatic parenchymal calculi are common, usually incidental, findings on morphological examinations. They are typically asymptomatic and may be present in association with normal glands, benign prostatic hyperplasia, and prostate cancer. However giant prostatic calculi are rare. Less than 20 cases have been reported in the literature. We present the case of a 35-year-old man with two giant prostatic calculi that replaced the entire gland. He underwent an open cystolithotomy, two giant stones were removed from the prostate, and we used a lithotripsy in situ for extraction of stone fragments.
Topics: Adult; Calcium Phosphates; Calculi; Hematuria; Humans; Male; Prostatic Diseases; Urethral Obstruction; Urinary Bladder; Urinary Retention
PubMed: 23565316
DOI: 10.11604/pamj.2013.14.69.2376 -
Nigerian Journal of Clinical Practice Sep 2022Prostate-specific antigen (PSA) is elevated in the serum of most men with prostatic diseases. Benign prostatic hyperplasia (BPH) is the commonest of these diseases. The...
BACKGROUND
Prostate-specific antigen (PSA) is elevated in the serum of most men with prostatic diseases. Benign prostatic hyperplasia (BPH) is the commonest of these diseases. The degree of enlargement of the prostate may determine the amount of PSA elaborated. Several reports in some parts of the world have shown a significant correlation between prostate volume (PV) and PSA. However, only a few reports have been documented in Nigeria, especially in the South-South region.
AIM
This research aimed to ascertain if there is any correlation between prostate volume (PV), total PSA (tPSA), and free PSA (fPSA) in men with histologically diagnosed BPH. This knowledge may help in the estimation of PV from a given PSA.
PATIENTS AND METHODS
This prospective hospital-based study was carried out in a southern Nigerian tertiary hospital between November 2017 and October 2018. Eighty (80) eligible and consenting patients participated in the study and were enrolled at first contact in the urology clinic. Each patient's blood was taken for PSA estimation. The prostate volume was estimated by transrectal ultrasound scan (TRUS). Those who had tPSA values greater than 4 ng/mL whose biopsy report showed prostate malignancy were excluded from the study. A proforma was used to collect patients' sociodemographic and clinical information. Data were entered and analyzed with Statistical Package for Social Sciences version 22 (SPSS Inc., Chicago, IL, United States). For all statistical tests, P < 0.05 was regarded as significant.
RESULTS
The mean age of the patients for this study was 68.03 years. The mean prostate volume was 87.9 mL with a range of 34 to 234 mL. The mean tPSA was 5.5 ng/mL with ranges of 1.1 to 21.1 ng/mL. There was a significant correlation between PV and tPSA with a P value of 0.0001. This correlation was also shown between PV and fPSA with a P value of 0.0001.
CONCLUSION
There is a statistically significant correlation between PV and PSA (both free and total) in men with symptomatic histologically diagnosed BPH. This finding showed that larger benign prostate glands elaborated greater amounts of PSA. It may, therefore, be appropriate to say that it is not in all cases of elevated serum tPSA that the possibilities of malignancy or inflammation should be entertained.
Topics: Aged; Humans; Male; Nigeria; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 36149214
DOI: 10.4103/njcp.njcp_67_22