雄激素受体CAG重复多态性与BPH和PCa相关性的meta分析

目的:通过meta分析探讨雄激素受体(AR)基因CAG重复多态性与良性前列腺增生(BPH)和前列腺癌(PCa)发病风险的关系。方法:检索国内外大型数据库发表的AR基因CAG重复多态性与BPH和PCa相关性的文献,基于异质性检验的结果,分别采用M-H固定效应模型和随机效应模型合并比值比(OR)效应量,采用Begg和Egger偏倚分析评估本项meta分析的发表偏倚,系统评价AR基因CAG重复多态性与BPH和PCa发病风险的关系,并按种族进行分层分析。结果:检索获得文献29篇,最终纳入4篇符合条件的文献,累计BPH患者485例、PCa患者767例、正常对照组709例。BPH组和正常对照组间不存在异质性,M-H固定效应模型合并效应量后提示低CAG重复多态性与BPH无相关性。PCa组和BPH组及对照组间均存在异质性,随机效应模型提示低CAG重复多态性与PCa的风险呈正相关(OR PCa/对照=1.45,OR PCa/BPH=1.86,OR PCa/(BPH+对照)=1.66)。种族分层的亚组分析提示,低CAG重复多态性与PCa发病风险在种族间存在差异。Begg和Egger偏倚分析显示各组比较中均无显著发表偏倚。结论:AR受体低CAG重复多态性与PCa发病风险呈正相关,与BPH发病风险无相关性。     

Inflammation and Chronic Prostatic Diseases: Evidence for a Link?

ObjectivesEmerging evidence indicates that prostatic inflammation may contribute to prostate growth either in terms of hyperplastic (benign prostatic hyperplasia [BPH]) or neoplastic (prostate cancer [PCa]) changes. We propose two questions: Does prostate inflammation represent a significant factor for the development and the progression of both BPH and PCa? Are data available now to sustain the identification of prostate inflammation as a risk factor for prostate diseases?MethodsWe reviewed the recent international literature using a PubMed search to analyze new findings supporting a role for inflammation in BPH and PCa growth and progression.ResultsOn histologic examinations from patients with BPH, inflammatory aspects are present in approximately 40% of cases. The men with inflammatory aspects inside the prostate have a significantly higher risk for BPH progression and acute urinary retention. Evidence shows that a cyclooxygenase-2 (COX-2) inhibitor can increase the apoptotic activity in human BPH tissue. Analyses on the bacterial colonization in PCa and normal prostate tissue showed a highly suggestive correlation between bacterial colonization/chronic inflammation and the diagnosis of PCa. Evidence from genetic studies supports the hypothesis that prostate inflammation may be a cause of PCa development. Proliferative inflammatory atrophy has been considered as an early histologic precursor to prostatic intraepithelial neoplasia and PCa.ConclusionThe concept that inflammation can promote chronic prostatic diseases, such as BPH or PCa, is actually supported by several new significant findings; however, no specific oncologic surveillance for these cases is justified at the moment.     

Why and How to Evaluate Chronic Prostatic Inflammation

ContextIn recent years, increasing scientific evidence has emerged to show that prostatic inflammation is one of the key predictive factors for benign prostatic hyperplasia (BPH).ObjectiveThis review describes the recent literature regarding the relationship between prostatic inflammation and BPH, and focuses on the clinical perspective of why and how to evaluate prostatic inflammation.Evidence acquisitionPublished literature relating to the role and evaluation of prostatic inflammation in BPH was identified by searching PubMed (Medline).Evidence synthesisLaboratory and clinical studies have demonstrated that prostatic inflammation is a central and relevant mechanism in prostate enlargement and BPH development. Despite the potential clinical use of predictive biomarkers such as interleukin-8, monocyte chemotactic protein-1, chemokine (C-C motif) receptor 7, cytotoxic T lymphocyte-associated antigen 4, inducible T-cell costimulator, and CD40 ligand, biopsy remains the standard procedure for evaluating prostatic inflammation histologically; however, biopsy can only be performed in patients with suspected prostate cancer. In the absence of biopsy data, prostatic calcification and symptom severity can assist clinicians in diagnosing suspected prostatic inflammation. Prostatic calcification has been shown to be present in 86% of symptomatic male patients aged >50 yr. Clinical data have also demonstrated that chronic inflammation and International Prostate Symptom Score are statistically significantly correlated, with storage symptoms being particularly strongly correlated with chronic inflammatory status. Furthermore, as the presence of metabolic syndrome has been shown to be highly correlated with lower urinary tract symptoms (LUTS) due to BPH (LUTS/BPH), clinicians need to consider metabolic syndrome accompanying chronic prostatic inflammation when evaluating patients for LUTS/BPH.ConclusionsChronic prostatic inflammation plays a central role in the pathogenesis and progression of BPH; therefore, it is important to evaluate it appropriately in patients with LUTS/BPH or suspected prostate cancer.     

单纯前列腺上皮内瘤回顾性分析(附142例病例分析)

目的通过对前列腺上皮内瘤(PIN)临床资料分析,探讨PIN的生物特性及应对策略。方法对31例无前列腺癌PIN(NPCaPIN)改变患者(其中1级23例,2、3级8例)的临床资料(包括患者血清PSA、fPSA/tPSA、PSA密度等区域计数资料以及穿刺标本免疫组织化学染色结果)进行回顾性分析,以同期确诊为前列腺癌(PCa)、良性前列腺增生(BPH)患者资料作为对照,分析低级别PIN(LGPIN)和高级别PIN(HGPIN)改变之间及NPCaPIN临床特征与PCa、BPH患者临床特征的差异。结果LGPIN和HGPIN改变的患者之间血清PSA水平和年龄存在差异(P<0.05);LGPIN和PCa患者之间血清PSA水平、前列腺体积、fPSA存在显著差异(P<0.01),PSA密度、fPSA/tPSA比值存在差异(P<0.05),和BPH患者之间各项均无明显差异;HGPIN改变和PCa患者之间前列腺体积、fPSA水平和年龄存在差异(P<0.05),和BPH患者之间血清PSA水平差异显著(P<0.01),fPSA/tPSA比值和年龄(P<0.05)存在差异;NPCaPIN和PCa患者之间血清前列腺体积、fPSA水平和年龄、血清PSA水平、PSA密度存在显著差异(P<0.01),和BPH患者之间fPSA/tPSA比值(P<0.05)存在差异。P63、AE1、AE3、P504S、PSA免疫组织化学结果NPCaPIN组类似于BPH而完全异于PCa。结论LGPIN的临床和病理特征与BPH相似,而HGPIN的临床和病理方面具有一定的前列腺恶性肿瘤特征,需要积极的临床追踪观察。     

Is There Evidence of a Relationship between Benign Prostatic Hyperplasia and Prostate Cancer? Findings of a Literature Review

Context

More than half the male population aged >50 yr have histologic evidence of benign prostatic hyperplasia (BPH), while prostate cancer (PCa) is among the most common male cancers according to recent registry data. Understanding the aetiologies of both conditions is crucial to reduce the resulting burden of mortality and morbidity.

Objective

This review aims to examine the available data on the epidemiology, pathology, risk factors, and genetic markers involved in BPH and PCa; to discuss their clinical implications for management of both conditions; and to discuss their implications for PCa prevention. Our primary objective was to clarify the relationship between BPH and PCa by bringing together evidence from diverse areas of research.

Evidence acquisition

The primary source of data was PubMed, which was searched using Boolean strategies and by scanning lists of related articles. We also examined secondary sources from reference lists of retrieved articles and data presented at recent congresses.

Evidence synthesis

Accumulating evidence suggests that BPH and PCa share important anatomic, pathologic, and genetic links in addition to the well-established epidemiologic association between these conditions. We also found data that suggest interactions between apparently diverse factors, such as dihydrotestosterone levels and inflammation. Recent publications support the hypothesis that both BPH and PCa are part of the metabolic syndrome, while inflammation is emerging as a major contributor to the development of both BPH and PCa. Although many of the findings are preliminary and require further research, they offer new insight into the mechanisms of disease underlying the development of BPH and PCa.

Conclusions

Available data suggest that epidemiologic and pathologic links exist between BPH and PCa. Evidence of links between the conditions and contributory factors may offer common preventative strategies for BPH and PCa and common therapeutic approaches to their management.     

Lymph and blood vessel architecture in benign and malignant prostatic tissue: lack of lymphangiogenesis in prostate carcinoma assessed with novel lymphatic marker lymphatic vessel endothelial hyaluronan receptor (LYVE-1)

PURPOSE: Due to the lack of specific markers the analysis of lymphatic vessel density (LVD) has been almost impossible in the past. We report the novel specific marker for lymphatic endothelium, lymphatic vessel endothelial hyaluronan receptor (LYVE-1), in prostatic, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissue. Normal blood vessels were additionally quantified in BPH and PCa. MATERIALS AND METHODS: LYVE-1 lymphatics (LVD) and CD34 blood vessels were assessed in 20 paraffin sections of BPH and 50 of PCa tissue by immunohistochemistry in a standardized experimental setting. The regions of PCa, periphery of the tumor and nontumorous regions of the PCa specimens, and BPH tissue were evaluated. Double staining was done (LYVE-1/CD34). Acquired data were interrelated and compared to the pathological parameters of the specimens. RESULTS: Double staining revealed numerous CD34 blood vessels but only a few LYVE-1 lymphatic vessels in BPH and PCa sections. Mean LVD +/- SD was distinctly lower (0.55 +/- 0.93) in PCa tissue than in tumor periphery (2.45 +/- 1.93) and nontumorous (3.16 +/- 2.23) tissue (p <0.0001). Maximum LVD was observed in BPH (7.17 +/- 3.61), which differed markedly from nontumorous areas of PCa specimens (p <0.001). In contrast to LVD, significantly more blood vessels were found in PCa (116.00 +/- 39.25) than in BPH (60.30 +/- 19.34) tissue (p <0.001). CONCLUSIONS: LYVE-1 is a specific lymphatic endothelial marker in benign and malignant prostate tissues. It is a useful new marker for the investigation of lymphatics. To our knowledge we report the immunohistochemical visualization and quantification of lymphatic vessels in prostatic tissue for the first time. In contrast to the stimulated angiogenesis of blood vessels in PCa, the destruction of lymphatic vessels occurs rather than lymphangiogenesis.     

BPH相关性抗原表达的临床意义

目的:探讨BPH相关性抗原(BPSA)在BPH、前列腺癌(PCa)诊断中的作用。方法:采用免疫组织化学ABC法,用BPSA单克隆抗体对62例BPH患者、37例PCa患者及30例其他肿瘤组织标本中的BPSA表达进行检测。结果:BPSA在100% BPH、88% PCa组织中呈不同程度的阳性表达,且在BPH组织中呈明显高表达。非前列腺肿瘤组织染色均呈阴性。组织BPSA表达与肿瘤病理分级无相关性(P>0. 05)。结论:BPSA具有良好的组织器官特异性,有助于早期PCa和BPH的鉴别诊断。     

经直肠彩色超声对前列腺癌诊断分析

目的：经直肠彩超检查,对照病理结果,探讨PCa的彩色多普勒超声表现和特征。方法：对经直肠彩超引导下穿刺活检确诊为PCa的30例患者35个恶性结节和BPH的25例患者42个增生结节的回顾,分析在二维声像图和彩色多普勒血流显像中的不同。结果：PCa结节出现在外周带为主,占86％（30／35）,内部以低回声多见,占88％（31／35）;BPH结节多出现在内腺,占81％（22／42）,内部高低回声均可见。BPH结节和PCa结节血供均增加,但PCa结节比BPH结节血流更丰富,动脉收缩期最高流速峰值、舒张末期血流峰速,加速指数、血流阻力指数明显增高,两者差异有统计学意义（P〈0．05）。结论：经直肠彩超有助于前列腺良恶病变的定性诊断,更有利于穿刺活检的准确定位。     

Review article Testosterone therapy in the ageing male: what about the prostate?

The concerns about testosterone therapy in ageing men with late-onset hypogonadism mainly address the risk of prostatic disease, i.e. either benign prostatic hyperplasia (BPH) or prostate cancer (PCa). Both conditions are highly dependent on androgen action and recent clinical data on the cancer-preventive effect of the 5alpha-reductase inhibitor finasteride have supported the possible role of androgens in PCa. However, the clinical data especially on the long-term effects of exogenous androgen substitution in regard to prostate safety are nonconclusive in many respects. As sufficient clinical studies on these risks will not be available in the near future, the approach of testosterone therapy towards prostate complications should be kept on a safe but practical basis. This review includes some recommendations in regard to testosterone therapy and prostate monitoring in patients with BPH and bladder outlet obstruction, with previous history of curative treatment for PCa or with prostatic intraepithelial neoplasia.     

The Link Between Benign Prostatic Hyperplasia and Inflammation

ContextBenign prostatic hyperplasia (BPH) is one of the most common diseases associated with the aging process in men, particularly men aged >50 yr, yet only a few predictive factors have been identified. In recent years, attention has focused on the role of prostatic inflammation in the pathogenesis and progression of BPH.ObjectiveThis article reviews recent findings related to the potential link between local and systemic inflammation and BPH.Evidence acquisitionIn March 2013, at the annual meeting of the European Association of Urology in Milan, Italy, a satellite symposium entitled “Benign Prostatic Hypertrophy (BPH) and Inflammation, from Lab to Clinic,” was held with the goal of reviewing the latest data relating to the link between inflammation and BPH. This paper is based on one of the presentations at this symposium. A structured PubMed literature search was performed, and emphasis was placed on results from the past 10 yr.Evidence synthesisBPH is characterized by progressive hyperplasia of stromal and glandular cells, and clinically it is defined by lower urinary tract symptoms. In recent years, there has been accumulating evidence linking prostatic inflammation with BPH. The inflammatory infiltrates observed in patients with BPH are composed primarily of chronically activated T-lymphocytes. Cytokines and growth factors released from inflammatory cells create a proinflammatory environment that may support the fibromuscular growth seen in BPH and may also be responsible for inducing a state of relative hypoxia as a result of the increased oxygen demand of the proliferating cells. A number of clinical studies have confirmed the presence of inflammatory infiltrate in men with BPH, and this infiltrate has been shown to be involved in the pathogenesis, clinical appearance, and progression of this disorder. There is evidence emerging that systemic inflammation may also play a role in BPH, since in men with metabolic syndrome there was a significant correlation between prostate diameter/volume and the number of metabolic syndrome components.ConclusionsIt is clear that a number of different mechanisms are involved in the development and progression of BPH. Prostatic inflammation is an important feature, since it appears to be involved in the pathogenesis, symptomatology, and progression of the disease.     

【原创论文】5—α还原酶在前列腺内的差异性表达及临床意义

人类良性或恶性前列腺疾病的发展与雄激素密切相关。雄激素主要包括睾酮（T）和双氢睾酮（DHT）。通过5-α还原酶（5-AR）的作用,睾酮转化成双氢睾酮。在人类良性和恶性前列腺组织中观察N5-α还原酶的表达具有差异性。5-α还原酶抑制剂（5-ARI）通常用于良性前列腺增生（BPH）的治疗,近年曾用于前列腺癌（PCa）的预防。本篇综述主要讨论在人类前列腺的正常发育和良性前列腺增生及前列腺癌发生与进展过程中,5-α还原酶差异性表达所发挥的作用。     

PSAD与PSAD-TZ在前列腺良、性疾病诊断中的应用价值

目的 :比较前列腺特异性抗原密度 (PSAD)、前列腺移行带抗原密度 (PSAD TZ)、前列腺特异性抗原 (PSA)及游离前列腺特异性抗原和总前列腺特异性抗原比值 (FPSA/TPSA)在良性前列腺增生 (BPH)和前列腺癌 (PCa)鉴别诊断中的作用。　方法 :4 3例BPH和 2 0例PCa病人 ,PSA均 <2 0 μg/L ,比较PSA、PSAD、FPSA/TPSA、PSAD TZ指标 ,并进行统计学分析。　结果 :BPH和PCa两组PSA平均值分别为 (10 .4 7± 6 .2 5 )、(13.92± 3.2 0 ) μg/L ,差异无显著性 (P >0 .0 5 )。两组PSAD平均值分别为 (0 .15± 0 .12 )和 (0 .2 4± 0 .13) ,差异有显著性 (P <0 .0 5 )。两组FPSA/TPSA平均值分别为 (0 .5 8± 0 .4 2 )和 (0 .2 6± 0 .17) ,差异有显著性 (P <0 .0 5 )。两组PSAD TZ平均值分别为 (0 .2 6± 0 .2 2 )和 (0 .5 1± 0 .2 8) ,差异具有非常显著性。 (P <0 .0 1)。　结论 :PSAD、FPSA/TPSA、PSAD TZ对PSA <2 0 μg/L的前列腺良恶性增生病人具有鉴别作用 ,其中尤以PSAD TZ更为准确     

Role of Prostatic Inflammation in the Clinical Presentation of Benign Prostatic Hyperplasia

ContextAlthough it was hypothesised >20 yr ago that prostatic inflammation could influence clinical presentation and possibly surgical outcome in patients with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), only more recently has compelling substantiating evidence become available.ObjectiveTo review the evidence for the role of inflammation in the clinical presentation and treatment of BPH/LUTS.Evidence acquisitionThis article is based primarily on material presented at a satellite symposium entitled, “Inflammation and Prostatic Diseases: From Bench to Bedside,” held during the 2015 annual meeting of the European Association of Urology in Madrid, Spain. Current data regarding the link between inflammation and BPH were reviewed.Evidence synthesisStudies such as the large-scale Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial and others have clearly demonstrated the association between the presence and/or degree of histologic inflammation and its impact on parameters such as prostate volume, voiding LUTS, and type of surgery required to treat BPH. Prostatic inflammation has been shown to increase by threefold the risk for acute urinary retention, an end point in the natural progression of BPH. Inflammation has been proposed as the common thread between the metabolic syndrome and BPH/LUTS, which frequently co-exist, and offers new therapeutic targets for medical treatment. Motivated patients can undertake lifestyle modifications (eg, weight, diet, exercise) to potentially prevent the need for surgery. Selective cyclooxygenase-2 inhibition appears promising as a therapeutic approach for inflammation, but its suitability for long-term use in the BPH population is limited by safety concerns.ConclusionsGreater understanding of the relationship between inflammation and the clinical presentation of BPH/LUTS provides an opportunity to effect clinical changes to improve treatment outcomes.Patient summaryAn increased understanding of the role of prostatic inflammation in the pathogenesis, symptomatology, and progression of benign prostatic hyperplasia (BPH) is likely to change the treatment paradigm for BPH.     

植物雌激素与前列腺癌及良性前列腺增生

植物雌激素是一类广泛分布于各类植物中的结构与雌激素相似并具有弱雌激素及抗雄激素活性的天然活性物质。PCa与BPH是雄激素依赖性及与年龄相关的疾病,近年来流行病学调查和实验研究均表明植物雌激素对PCa与BPH有防治作用。其机制可能与植物雌激素对性激素的调节、对细胞增生的抑制、诱导细胞凋亡及抗氧化作用等有关。     

前列腺癌与良性前列腺增生差异表达基因的研究

目的 :筛选和分析前列腺癌 (PCa)与良性前列腺增生 (BPH)组织中差异表达的基因。　方法 :应用含有 4 6 5个基因的寡聚核苷酸芯片 ,检测PCa和BPH组织中差异表达的基因。　结果 :PCa和BPH组织中表达差异有显著性的基因共 35个 ,PCa上调基因 1 7个 ,下调 1 8个。　结论 :PCa与BPH组织差异表达基因的研究 ,有助于了解PCa发生发展的分子机制和寻找PCa新的诊断治疗标志物。     

良性前列腺增生、前列腺癌组织内皮素-1的表达及其意义

目的:探讨内皮素1(ET-1)在BPH及PCa中的表达及其临床意义。方法:应用免疫组化ElivisionTM plus法对36例BPH和44例PCa组织中ET-1分别进行免疫组化染色,并在光镜下判断染色部位和染色强度。结果:ET-1在BPH和PCa组织中阳性表达率为100%;阳性染色部位主要位于肿瘤和增生的腺上皮的胞质,以及间质平滑肌细胞胞质;间质血管内皮细胞染色均为阳性;比较BPH和PCa的ET-1表达强度,两者差异无显著性(P>0.05);低分化PCa的ET-1表达强度显著高于高、中分化PCa(P<0.01);在骨转移(BM)PCa和非骨转移(non-BM)癌之间,ET-1表达强度差异无显著性(P>0.05)。结论:ET-1在BPH和PCa组织中均有高比例的表达,且两者的表达定位相同。ET-1与BPH和PCa的发生发展均有一定的相关性。     

EGFR和ABS在前列腺增生和癌变组织中的表达及意义

为探讨前列腺增生和前列腺癌的病因及发病机制，应用免疫组织化学ＳＰ法检测了１４例正常前列腺、６０例前殓腺增生和３３例前列腺癌组织中表达生长因子受体和雄激素结合位点的表达。结果显示，前列腺增生和前列腺癌组织中ＥＣＦＲ阳性表达率明显高于正常组织；前列腺癌中ＡＢＳ的阳必明显高于增生和正常组织，而增生组织中，ＡＢＳ强阳性率又明显高于正常组织。ＥＧＦＲ表达与肿瘤病理分级呈正相关，而与ＡＢＳ表达无相关。ＥＧＦＲ     

血清结合PSA对前列腺疾病诊断价值的探讨

目的 :探讨血清中结合前列腺特异性抗原 (cPSA)在前列腺癌 (PCa)诊断中的临床价值。　方法 :用磁微粒子免疫化学发光法测定 110例良性前列腺增生 (BPH)病人和 78例PCa病人cPSA、tPSA ,并计算cPSA/tPSA比值。　结果 :cPSA及cPSA/tPSA比值可有效地区分BPH和PCa(P <0 .0 0 5 ) ,尤其是在诊断灰值区 (tPSA为 4～10 μg/L)时效果更显著。在以tPSA≤10 .0 μg/L和cPSA/tPSA≥0 .78为筛选界值联合对PCa进行筛选时 ,临床概率敏感度为 97.8%,特异性为 95 .8%,阴性预示值为 81.9%,阳性预示值为 96 .5 %。　结论 :cPSA的引入及cPSA/tPSA比值的应用 ,对PCa的诊断具有重要临床意义 ,尤其是在tPSA的诊断灰值区。