Tissue type plasminogen activator as a marker for functional zones, within the human prostate gland

The cellular distribution of tissue plasminogen activator in the prostate central zone, prostate peripheral zone, and seminal vesicle was studied by using immunohistochemistry. Samples of these three regions were taken from 20 radical prostatectomy specimens. Sixteen of 18 central zone samples showed positive staining of 20-90% of the epithelial cells. All 15 peripheral zone samples were negative, and only three of 14 seminal vesicles showed positive staining, which was present in less than 5% of cells. The distribution of tissue plasminogen activator within the prostate was the same as that previously reported for pepsinogen II. This suggests that the central zone of the prostate may be the selective site of origin for proteolytic enzymes in seminal fluid.     

Anatomy of the prostate: An historical survey of divergent views

Historically, the study of the prostate anatomy has been characterized by a proliferation of contradictory findings. The major divergent views of prostate anatomy are here reviewed and compared in order to facilitate further study and the ultimate selection of the best anatomical model. The details of Lowsley's original concept of the prostate lobes and the subsequent evolution of this concept into several contradictory hypotheses are traced. Discrepancies between the findings of Lowsley, Franks, and McNeal are explained. Conclusions are drawn which may facilitate the further study of anatomy and disease in both the human animal prostate.     

Impact of the static prostatic urethral angle on men with lower urinary tract symptoms

ObjectiveThe purpose of this study was to investigate the relationship between the prostatic urethral angle (PUA) and the peak urinary flow rate (Q_max), as well as the severity of lower urinary tract symptoms (LUTS) in men with benign prostate hyperplasia.Materials and methodsThe records of first-visit male patients with LUTS in the outpatient department of our institution were obtained. A transrectal ultrasound was performed on these patients after a detailed physical examination and medical history taking were performed. The International Prostate Symptom Score (IPSS) of the patients, the prostate size, the length of intravesical prostatic protrusion (IPP), and the PUA were evaluated. The patients also underwent uroflowmetry and bladder scan for residual urine.ResultsA total of 227 patients were included in this study. The mean PUA was 44.58 ± 12.87°. The mean prostate volume was 39.39 ± 19.79 mL, and the mean IPP was 4.82 ± 6.82 mm. After utilizing multivariate linear regression analysis, PUA was independently associated with IPSS (p < 0.001) and Q_max (p < 0.001). However, prostate volume and IPP were not associated with the above clinical items. None of the prostatic parameters were associated with the amount of postvoiding residual urine.ConclusionPUA has a remarkable correlation with Q_max and IPSS in men with LUTS. As PUA increased, IPSS also increased, and urinary flow rate decreased, exhibiting an inverse relationship.     

Course of localized adenocarcinoma of the prostate treated by radical prostatectomy

Among 562 patients with histologic stage B-1, B-2, or C adenocarcinoma of the prostate treated by radical prostatectomy and pelvic lymphadenectomy, analysis revealed that increasing histologic stage, tumor size, degree of capsular invasion, seminal vesicle involvement, and histologic grade all were highly correlated with both local and systemic progression (log-rank two-sided P less than or equal to 0.0001). No variable correlated with survival--a result that may reflect appropriate adjuvant therapy given at the time of progression. The death rate from prostatic cancer did appear to rise progressively with increase of stage. Overall, the projected 10-year survival was 76%.     

Reference ranges for serum prostate-specific antigen in black and white men without cancer

Objectives. To determine the age- and race-specific prostate-specific antigen (PSA) distributions in healthy men in central South Carolina and to compare these to data from other studies.Methods. Two thousand ninety-two black men aged 40 to 69 years and white men aged 50 to 69 years from the general population in 11 counties of central South Carolina participated in a prostate cancer educational program. Seventy-two percent of the participants were black—about double the proportion in the general population—and 63% of the men (1319 of 2092) subsequently obtained a PSA determination from their own physician. The distribution of serum PSA was compared with distributions from the Olmsted County study and from the Walter Reed Army Medical Center/Center for Prostate Disease Research study.Results. Older men without cancer had higher PSA levels. Regression analyses yielded an associated increase of about 3.3% per year. Reference ranges for normal PSA in men without cancer (based on their sample 95th percentiles) were zero to 1.9, 3.8, and 5.7 ng/mL in black men aged 40 to 49, 50 to 59, and 60 to 69 years, and zero to 2.7 and 4.9 mg/mL in white men aged 50 to 59 and 60 to 69 years, respectively.Conclusions. Reference ranges for normal serum PSA levels should take into account the population from which they are derived and to which they will be applied. Reference ranges that are useful in the general population can differ from those that are appropriate in a hospital setting. For the general population in central South Carolina, reference ranges for serum PSA levels are lower than previously published reference ranges, particularly among black men.     

Other biomarkers for detecting prostate cancer

Prostate‐specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase‐type plasminogen activator receptor, prostate‐specific membrane antigen, early prostate cancer antigen, PCA3, α‐methylacyl‐CoA racemase and glutathione S‐transferase π hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.     

Expression of prostatic TRH-like peptides differs between species and between malignant and nonmalignant tissues

Thyrotropin-releasing hormone-immunoreactive peptides (iTRH) were analyzed in normal rat and rabbit prostates and in human benign prostatic hyperplasia (BPH) and prostate cancer. Peptides were extracted from tissues, fractionated by anion and cation exchange chromatography, and analyzed by TRH radioimmunoassay. pGlu-Glu-Pro-NH₂ predominated in rabbit, but accounted for only 10–15% of iTRH in rat and human BPH. Uncharged peptides predominated in rat and human prostate. Authentic TRH (pGlu-His-Pro-NH₂) is not present in rabbit prostate, but may account for up to 25% of iTRH in rat and human prostate. iTRH was virtually absent in prostate cancer. These results demonstrate considerable heterogeneity in the expression of TRH-like peptides in the prostates of various animal species, and suggest decreased expression of these peptides in prostate cancer. © 1993 Wiley-Liss Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America

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Which is the best radiological imaging method for predicting actual prostate weight?

In this study, we compared the weight of the prostate specimen removed after robotic radical prostatectomy with the prostate weight measured pre-operatively by four different imaging modalities. Pre-operative prostate weight before robotic radical prostatectomy was measured by Transabdominal Ultrasonography (TAUS), Transrectal Ultrasonography (TRUS), Abdominal Tomography (CT) and MultiparametricProstate Magnetic Resonance imaging (mpMRI). Of the 170 patients enrolled in the study, the mean age was 65.2 ± 7.08 (46–84) years and mean prostate-specific antigen (PSA) 9.6 ± 7.7 (1.8–50). The mean post-operative actual prostate weight was 63.1 ± 30 gr. The mean pre-operative prostate volumes measured by TAUS, TRUS, CT and MPMRI were 64.5 ± 28.5, 49.1 ± 30.6, 54.5 ± 30.5 and 68.7 ± 31.7 ml, respectively (p < .001). Post-operative actual prostate weight correlated with prostate weight measured by TAUS, TRUS, CT and mpMRI (r coefficient 0.776, 0.802, 0.768 and 0.825 respectively). The best of these was mpMRI. Although prostate weight measured by different imaging methods has a high correlation to predict actual prostate weight, actual prostate weight is best predicted by measurements with mpMRI. However, errors and deviations that may occur with these imaging methods should be taken into consideration.     

Androgen Interaction with the Polyamine System of the Rat Prostate

The ventral and dorsal lobes of the rat prostate contain larger quantities of the aliphatic amines putrescine, spermidine and spermine and higher activities of the enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) than other accessory sex glands. In contrast, the coagulating glands and the seminal vesicles contain only small quantities of the amines but the highest activities of the arginase (ARG; EC 3.5.3.1). Lineweaver-Burk plots indicated that the Km-values for ARG in the coagulating gland and ODC in the ventral prostate lobe were 20 mM and 0.2 mM, respectively. Castration decreased ODC and ARG activities to 3 and 50% of control levels, respectively, after 3 days, whilst the Km-values were unaffected. Daily administration of 3 mg dihydrotestosterone (DHT) prevented these castrational changes. Oestrogen treatment alone had no effect on the activities of the enzymes, but appeared to exert a synergistic effect with androgen on the ODC. Administration of androgen to intact rats for 7 days caused a dose-related alteration in the ratios of the various amines, particularly the spermine: putrescine ratio. A minor but significant decrease was also recorded in the activity of the ODC, which was mirrored by an increase in the levels of putrescine in the tissue. The data suggest that androgen control of the polyamine pathway is biphasic, first stimulatory and later inhibitory with lesions occurring at the ODC, possibly via short loop feedback of its product putrescine, but also at subsequent enzymic steps in spermidine and spermine biosynthesis.     

超声引导下前列腺12针系统穿刺活检增加前列腺癌检出率的研究

目的:探讨不同年龄及前列腺特异性抗原(PSA)分组对12针穿刺活检前列腺癌检出率及肿瘤特征的影响。方法:临床表现怀疑前列腺癌患者210例,按照患者的年龄分为≤59岁组、60～69岁组、70～79岁组、≥80岁组,按照PSA水平分为0～4μg/L组、4.1～10μg/L组、10.1～20μg/L组、20.1～50μg/L组、>50μg/L组,记录患者临床资料及活检结果。提出不同的穿刺方案并计算其检出率。结果:210例怀疑为前列腺癌患者,检出前列腺癌91例,总的前列腺癌检出率为43.3%,随着年龄的增长,PSA水平的提高,检出率逐渐提高。年龄的增长、PSA水平的提高与体积较大、分级较高的肿瘤密切相关。外周带穿刺与旁正中矢状尖部穿刺有较高的前列腺癌检出率。当患者年龄<60岁,PSA水平<20μg/L时,12针穿刺活检为较佳方案。结论:12针穿刺活检可以弥补6针穿刺活检的缺陷,随着患者年龄的增长,PSA水平的提高,肿瘤的体积增大、病理分级较差。传统6针穿刺法与12针相比,受患者年龄、PSA水平的影响较大。     

Polarity of prostate specific membrane antigen,prostate stem cell antigen,and prostate specific antigen in prostate tissue and in a cultured epithelial cell line

BACKGROUND: Madin-Darby canine kidney (MDCK) cells are immortalized epithelial cells that have been used extensively as a model system to study intracellular molecular trafficking, polarized expression, and secretion of proteins in various epithelia. In order to determine if MDCK cells might serve as a model to study molecular events within prostate epithelial cells, we have evaluated the polarized distribution of three prostate restricted proteins, PSMA, PSCA, and PSA, in situ, and in MDCK cells. METHODS: Using immunofluorescence, confocal microscopy, cell surface biotinylation, antibody internalization, and biochemical assays we evaluated surface expression and secretion of three prostate restricted proteins expressed in MDCK cells. We compared these patterns of expression to results observed within prostatic epithelium. RESULTS: We demonstrate that PSMA is localized primarily to the apical plasma membrane in both the prostatic epithelium and transfected MDCK cells, whereas PSCA is expressed in a non-polarized fashion. We also show that PSA is secreted predominantly from the apical surface of transfected MDCK cells, consistent with in vivo observations. CONCLUSIONS: Similar patterns of localization among MDCK and prostatic epithelial cells suggest that the mechanisms of polarized sorting within these cell types are conserved. Thus, MDCK cells offer a useful model system to study mechanisms of targeting of these proteins within the prostate.     

前列腺体积及前列腺穿刺针数对前列腺癌诊断的影响

目的探讨前列腺体积及前列腺穿刺针数对前列腺癌诊断情况的影响并分析其原因。方法回顾性总结2002∽2009年间于我院行超声引导下经直肠前列腺系统12针穿刺292例患者的临床资料。患者PSA在o～20ng／mL之间。经直肠超声计算前列腺体积。将患者按照前列腺体积分为：〈30mL,30∽60mL,60∽90mL,〉90mL四组,比较各组前列腺穿刺6针、8针、10针、12针时前列腺癌诊断率。统计学Fisher’S检验比较各组间差异性。结果总体前列腺癌诊断率为25％（73／292）,在〈30mL组：6针、8针、10针、12针的前列腺癌诊断率相同,均为39．13％（21／54）;在30～60mL组：6针、8针、10针、12针的诊断率分别为：21．3％（23／108）、23．1％（25／108）、23．1％（25／108）、24．1％（26／108）,诊断率无显著差异（P〉0．05）。在60～90mL组：6针的诊断率为12．9％（12／93）,显著低于8针（19．4％（18／93）3、10针[20．4％（19／93）]、12针（20．4％（19／93）]的诊断率（Pd0．05）。在〉90mL组：6针、8针的诊断率均为8．1％（3／37）,显著低于10针、12针的诊断率C18．9％（7／37）,P〈0．053。黠论前列腺体积是选择前列腺穿刺针数时的一个重要的参考因素,在前列腺体积较大的情况下,可适当的增加前列腺穿刺针数,在前列腺体积较小的情况下,增加前列腺穿刺针数并不能提高前列腺癌的诊断率。     

Review: prostate cancer epidemiology

Prostate cancer is common among men in the United States. Factors of possible importance in the etiology of prostate cancer include diet, primarily implicated by ecologic studies of national, regional, and ethnic variation in rates; endocrine function, implicated by the importance of endocrine function in normal prostatic growth and in the treatment of prostate cancer; genetic susceptibility, supported by familial aggregation; some aspect of sexual behavior, suggested by case-control differences in sexual behavior; and occupational exposure, particularly cadmium exposure. Despite the public health importance of prostate cancer, it has received only moderate epidemiologic study; thus the etiologic importance of these and other possible determinants of prostate cancer risk is uncertain [55].     

Neuroendocrine differentiation of human prostatic primary epithelial cells in vitro

BACKGROUND: Dispersed prostatic neuroendocrine cells are involved in growth regulation of the prostate and are considered to play a role in the pathogenesis of prostate carcinoma and benign prostatic hyperplasia (BPH). They are meant either to be derived from the neural crest during embryogenesis or by direct differentiation of the cells from locally present precursor cells. METHODS: An in vitro model was developed for human prostatic epithelial and neuroendocrine cell differentiation. Minced explants from radical prostatectomies were seeded on collagen I-coated plates. RESULTS: The majority of outgrowing cells were basal cells, positive for cytokeratin markers K 5/14 and CD 44, as determined by confocal laser scanning microscopy. A small fraction of interdispersed single cells expressing c-kit, which is found on pluripotent precursors, was identified by immunofluorescence. From these basal cells, in vitro differentiation of cells with neuroendocrine morphology could be achieved within 3 days. These were at rest, i.e., non-bromodeoxyuridine incorporating cells and characteristically coexpressed K 5/14, K 18, and the neuroendocrine marker chromogranin A. Luminal cells staining for K 8 or 18 were not observed. CONCLUSION: Neuroendocrine differentiation of adult prostatic cells was achieved in vitro, favoring the hypothesis that neuroendocrine cells are derived from peripheral precursor cells. The acceleration of this differentiation pathway may be the reason for the increased presence of neuroendocrine cells in areas of epithelial hyperplasia in BPH.     

Differential gene expression profiling of functionally and developmentally distinct human prostate epithelial populations

BACKGROUND

Human fetal prostate buds appear in the 10th gestational week as solid cords, which branch and form lumens in response to androgen 1. Previous in vivo analysis of prostate epithelia isolated from benign prostatectomy specimens indicated that Epcam⁺CD44^?CD49f^Hi basal cells possess efficient tubule initiation capability relative to other subpopulations 2. Stromal interactions and branching morphogenesis displayed by adult tubule‐initiating cells (TIC) are reminiscent of fetal prostate development. In the current study, we evaluated in vivo tubule initiation by human fetal prostate cells and determined expression profiles of fetal and adult epithelial subpopulations in an effort to identify pathways used by TIC.

METHODS

Immunostaining and FACS analysis based on Epcam, CD44, and CD49f expression demonstrated the majority (99.9%) of fetal prostate epithelial cells (FC) were Epcam⁺CD44^? with variable levels of CD49f expression. Fetal populations isolated via cell sorting were implanted into immunocompromised mice. Total RNA isolation from Epcam⁺CD44^?CD49f^Hi FC, adult Epcam⁺CD44^?CD49f^Hi TIC, Epcam⁺CD44⁺CD49f^Hi basal cells (BC), and Epcam⁺CD44^?CD49f^Lo luminal cells (LC) was performed, followed by microarray analysis of 19 samples using the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data was analyzed using Partek Genomics Suite Version 6.4. Genes selected showed >2‐fold difference in expression and P < 5.00E‐2. Results were validated with RT‐PCR.

RESULTS

Grafts retrieved from Epcam⁺CD44^? fetal cell implants displayed tubule formation with differentiation into basal and luminal compartments, while only stromal outgrowths were recovered from Epcam‐ fetal cell implants. Hierarchical clustering revealed four distinct groups determined by antigenic profile (TIC, BC, LC) and developmental stage (FC). TIC and BC displayed basal gene expression profiles, while LC expressed secretory genes. FC had a unique profile with the most similarities to adult TIC. Functional, network, and canonical pathway identification using Ingenuity Pathway Analysis Version 7.6 compiled genes with the highest differential expression (TIC relative to BC or LC). Many of these genes were found to be significantly associated with prostate tumorigenesis.

CONCLUSIONS

Our results demonstrate clustering gene expression profiles of FC and adult TIC. Pathways associated with TIC are known to be deregulated in cancer, suggesting a cell‐of‐origin role for TIC versus re‐emergence of pathways common to these cells in tumorigenesis. Prostate 75: 764–776, 2015. © The Authors. The Prostate, published by Wiley Periodicals, Inc.

     

血清前列腺特异抗原测定的临床意义

以12例前列腺癌、102例前列腺良性增生(BPH)、16例直肠指检(DRE)异常、5例前列腺炎及30例正常男性为对象,用酶免法测定血清前列腺特异抗原(Prostate specific antigen,PSA)浓度,用放免法测定其中37例。前列腺癌的PSA浓度明显高于BPH(P<0.01),PSA对前列腺癌诊断的敏感性为91.7％。DRE异常者大于BPH(P<0.05),低于前列腺癌(P<0.01)。BPH高于正常对照(P<0.01)。前列腺切除术后一日的PSA高于术前(P<0.01),术后6～8日同术前无显著性差异(P>0.05)。70岁以上高于70岁以下(P<0.05)。PSA>10ng/ml时酶免检测值低于放免法(0.010.05)。单纯PSA升高并不能说明任何特异性病理过程,前列腺癌的诊断,应结合PSA系列测定值及DRE和经直肠B超(TRUS)来综合分析。