前列腺癌组织中前列腺癌抗原-1的表达及临床意义

目的:探讨PCa组织中前列腺癌抗原-1(PCA-1)的表达及其临床意义。方法:采用逆转录-聚合酶链反应(RT-PCR)技术,检测45例PCa组织、30例前列腺高分级上皮样内瘤样病变组织(HG-PIN)、43例BPH组织和39例其他肿瘤组织标本中PCA-1 mRNA的表达。免疫组织化学检测不同前列腺组织中PCA-1蛋白的表达。结果:PCa与HG-PIN组织标本中PCA-1 mRNA的阳性表达率分别为80.0%(36/45)和60.0%(18/30),BPH组织及其他肿瘤组织中均未见PCA-1 mRNA的表达。PCA-1 mRNA表达与PCa的临床病理参数之间无明显相关性,差异均无统计学意义(P>0.05)。PCa与HG-PIN组织标本中PCA-1蛋白的阳性表达率分别为75.6%(34/45)和50.0%(15/30),BPH组织及其他肿瘤组织中未见PCA-1蛋白阳性表达。结论:PCA-1仅在PCa组织中表达,且与PCa的临床病理参数无关,有可能作为特异性的肿瘤标志物对PCa进行早期诊断。     

Prostate cancer antigen-1 as a potential novel marker for prostate cancer

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.     

前列腺癌组织中P504S的表达及其与血清前列腺特异抗原的关系

目的 探讨α-甲酰基辅酶A消旋酶(P504S)在前列腺癌(PCa)组织中的表达及其与血清PSA的关系.方法 采用免疫组织化学方法 检测P504S在PCa(36例)、前列腺高分级上皮样内瘤样病变(HG-PIN,20例)及良性前列腺增生(20例)组织中的表达,探讨其在PCa中的表达水平与血清PSA水平的关系.结果 36例PCa组织标本中,P504S的表达阳性率为72.2%(26/36).20例HG-PIN组织中P504S的表达阳性率为55.0%(11/20),20例良性前列腺增生组织中均未见阳性表达.高分化、中分化、低分化PCa组织中P504S的阳性表达率分别为44.4%、72.2%、100.0%.P504S表达与PCa恶性程度呈正相关(P＜0.05),与患者血清PSA水平无明显相关(P＞0.05).结论 P504S基因表达与Pea的分级密切相关.     

前列腺癌中PIM-1的表达及其临床意义

目的 探讨PIM-1在前列腺癌中的表达及临床意义。方法 逆转录-聚合酶链反应（RT—PCR）半定量分析2例良性前列腺增生（BPH）和5例前列腺癌（PCa）组织标本中PIM-1mRNA表达，免疫组织化学法检测20例BPH、20例高分级前列腺上皮内瘤（HGPIN）和42例PCa组织标本中PIM-1蛋白表达水平，染色结果分为阴性、弱阳性、阳性和强阳性。结果 5例PCa组织PIM-1mRNA表达相对值分别为0．63、0．55、0．42、0．91、0．76，2例BPH中其相对值为0．26、0．27。BPH、HGPIN和PCa组织中PIM-1蛋白阴性表达率分别为60％（12／20）、20％（4／20）和2％（1／42），弱阳性表达率分别为40％（8／12）、20％（4／20）和12％（5／42），阳性列强阳性表达率分别为0（0／20）、60％（12／20）和86％（36／42），PCa中PIM-1蛋白表达水平高于HGPIN和BPH（P值均〈0．05）。PIM-1蛋白表达水平随PCa的临床分期和病理分级增高而增强，在有和没有淋巴结转移PCa组织中PIM-1强阳性表达率分别为70％（7／10）、25％（8／32），差异有统计学意义（P〈0．05）。结论PIM-1高表达可能与PCa发生和发展相关，PIM-1表达水平与PCa分期、Gleason评分呈正相关，可能成为PCa预后判断的肿瘤标志物。     

前列腺癌患者前列腺液中DD3 mRNA检测及临床意义

目的检测前列腺癌（PCa）患者前列腺液中DD3基因的表达,讨论其临床意义。方法收集31例PCa患者、59例前列腺增生（BPH）患者前列腺液,离心取细胞沉淀物,提取总RNA,采用逆转录-聚合酶链反应（RT-PCR）琼脂糖电泳法方法检测其中DD3 mRNA的水平。同时用2χ检验分析比较不同Gleason分级的PCa患者DD3 mRNA阳性率是否存在差异。结果 PCa患者前列腺液中DD3 mRNA阳性率（77.42%）明显高于BPH患者（5.08%）,两者具有显著性差异（P〈0.01）。DD3 mRNA表达阳性率诊断PCa的灵敏度为77.42%,特异度为94.91%,不同Gleason分级的PCa患者DD3 mRNA表达阳性率无显著统计学差异（P〉0.05）。结论检测前列腺液中DD3 mRNA诊断PCa是一种有效的无侵入性的良好方法。     

Mcl-1和Caspase-3在前列腺癌患者中的表达和意义及相关性分析

目的 观察Mcl-1和Caspase-3在前列腺癌（PCa）、良性前列腺增生（BPH）组织中的表达情况,探讨两者相关性及意义。方法 采用免疫组化法检测并比较分析30例BPH和35例不同病理分级的PCa组织切片Mcl-1、Caspase-3蛋白的表达。结果 PCa组Mcl-1阳性表达率为82.86%（29/35）,显著高于BPH组13.33%（4/30,P<0.05）;PCa组Caspase-3阳性表达率为25.71%（9/35）,显著低于BPH组73.33%（22/30）（P<0.05）。Mcl-1、Caspase-3蛋白的表达与PCa患者术前PSA值、有无远处转移、Gleason评分、临床分期等临床资料无关(P>0.05)。在PCa组织中Mcl-1的表达与Caspase-3的表达呈负相关（r_s=-0.748,P<0.05）。结论Mcl-1、Caspase-3在PCa的发生、发展中可能相互影响。     

前列腺增生与前列腺癌中KLK11/TMPRSSmRNA表达比值

目的 以实时荧光定量PCR技术测定前列腺增生(BPH)与前列腺癌(PCa)组织标本KLK11/TMPRSS mRNA比值,探讨KLK11/TMPRSS比值在前列腺癌诊断的特异性意义.方法 通过实时荧光定量PCR对23例PCa、37例BPH及3例正常前列腺组织KLK11/TMPRSS的表达,比较其在PCa与BPH中组织定量的差异.结果 BPH与PCa组织KLK11/TMPRSS mRNA的定量表达值分别为2.264±0.460与5.905±0.780,差异有统计学意义(P＜0.05).结论 实时荧光RTPCR定量检测KLK11/TMPRSS mRNA为前列腺癌的诊断提供了可靠的辅助指标.     

实时荧光定量聚合酶链反应检测前列腺癌中Id1 mRNA的表达及意义

目的 检测Id1 mRNA在人前列腺癌（PCa）组织中的表达，探讨Id1 mRNA的表达与临床意义。方法 用SYBR Green Ⅰ嵌合荧光法进行实时逆转录-聚合酶链反应（RT—PCR），检测Id1 mRNA在人正常前列腺、前列腺良性增生（BPH）和PCa组织中的相对定量，分析Id1 mRNA的相对含量与PCa临床病理参数间关系。结果 Id1 mRNA在PCa组织中的含量明显高于BPH组织（P〈0．01）。Id1 mRNA表达量与PCa的Gleason评分有明显相关性（r=0．9995，P〈0．05）。Id1 mRNA表达量高者，2年内发生浸润和转移的机率提高。结论 PCa组织中Id1 mRNA表达明显增高，与肿瘤分化程度成负相关，Id1 mRNA的高表达从转录水平反映了其与前列腺癌病情进展的关系；Id1 mRNA的实时定量检测有助于从转录水平对前列腺癌进行早期诊断并初步指导预后。     

DD3 mRNA在前列腺癌组织中定量表达分析

目的:探讨DD3基因在前列腺组织中表达的临床意义。方法:用荧光定量RT-PCR方法对21例前列腺癌(PCa)组织、27例非前列腺部位的肿瘤组织、39例良性前列腺增生(BPH)组织和15例正常前列腺组织中的DD3的表达进行了定量分析,用ROC曲线对DD3 mRNA诊断PCa的性能进行了分析。结果:27例非前列腺组织中均未检测到DD3基因的表达。DD3在PCa组、BPH组和正常前列腺组表达量的中位数分别为7.2×106、2.5×104、1.5×104拷贝/mg组织。PCa组较BPH组和正常前列腺组DD3的表达量显著增高(P<0.01),而BPH组和正常前列腺组间则差异无显著性(P>0.05)。DD3表达量与临床分期和分化程度之间均无明显相关性。DD3 mRNA曲线下面积(AUC-ROC)为0.937(95%CI:0.879～0.995)。当临界值为1.4×105拷贝/mg组织时,灵敏度、特异度、准确度、阳性预测值(PPV)、阴性预测值(NPV)、阳性拟然比(+LR)、阴性拟然比(-LR)分别为90.5%、85.0%、86.7%、76.0%、94.3%、6.03和0.11。结论:DD3 mRNA的表达仅限于前列腺组织,具有良好的组织特异性。DD3 mRNA表达在PCa组织中显著升高,在正常前列腺和BPH组织中差异无显著性。DD3 mRNA可作为PCa诊断的良好标志物,在PCa早期诊断、微转移诊断、预后判断、指导治疗等方面也具有潜在的应用价值。     

转录因子FOXO1在前列腺癌组织中的表达及临床意义

目的:检测前列腺癌(PCa)组织与良性前列腺增生(BPH)组织中转录因子FOXO1的表达情况,探讨FOXO1与PCa临床病理参数之间的关系。方法:收集2010年1月～2016年12月我院53例PCa患者行根治性前列腺切除术后病理标本和经尿道前列腺电切术的53例BPH病理标本,采用组织芯片方式收集组织标本,使用免疫组化染色法检测FOXO1表达情况,分析FOXO1表达同PCa患者临床病理参数之间的关系。结果:BPH组织中FOXO1呈高表达,PCa组织中FOXO1表达显著低于BPH组织(39.6%vs.86.8%,P0.05),中低危PCa组织的相对表达量显著高于高危PCa组织(P0.05)。FOXO1表达与PCa PSA水平、病理T分期、淋巴结转移、Gleason评分显著相关(P0.05),Gleason评分越高FOXO1水平越低,PCa组织中FOXO1表达与患者年龄、前列腺体积、切缘阳性无明显相关性(P0.05)。结论:FOXO1在PCa组织中异常低表达,与PCa侵袭转移相关,FOXO1表达与PCa PSA水平、病理T分期、淋巴结转移和Gleason评分密切相关。     

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019

BackgroundInnovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.ObjectiveTo present the results from the APCCC 2019.Design, setting, and participantsSimilar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitationsPanellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.ConclusionsThese voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.     

DNA甲基化与前列腺癌

DNA甲基化是恶性肿瘤普遍存在的分子生物学改变,与肿瘤的发生和发展密切相关。前列腺癌中存在多种基因的甲基化,涉及到DNA损伤修复、激素应答、肿瘤细胞入侵/转移、细胞周期调控等通路。前列腺癌前病变如前列腺上皮内瘤也存在DNA甲基化,但程度相对较低。DNA甲基化的研究为前列腺癌的早期诊断、预后评估及激素非依赖性前列腺癌的治疗提供了新的途径。     

DNA甲基化与前列腺癌

DNA甲基化是恶性肿瘤普遍存在的分子生物学改变，与肿瘤的发生和发展密切相关。前列腺癌中存在多种基因的甲基化，涉及到DNA损伤修复、激素应答、肿瘤细胞入侵／转移、细胞周期调控等通路。前列腺癌前病变如前列腺上皮内瘤也存在DNA甲基化，但程度相对较低。DNA甲基化的研究为前列腺癌的早期诊断、预后评估及激素非依赖性前列腺癌的治疗提供了新的途径。     

缺氧诱导因子-1与前列腺癌研究进展

缺氧诱导因子-1(HIF-1)与前列腺癌存在密切的关系。研究表明HIF-1在前列腺癌中不但与血管生成因子、增殖与存活因子、葡萄糖转运以及糖分解酶等有关,而且与p53、p21、信号转导通路等有关。通过对HIF-1的深入研究将对前列腺癌的诊断与治疗提供新的思路。现对HIF-1的结构、功能及与前列腺癌关系进行综述。     

Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017

Background

In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics.

早期前列腺癌的诊断与治疗

随着前列腺癌发病率在我国的逐年升高,泌尿外科医生对此疾病的早期诊断与治疗也越来越关注。尽管美国的资料显示前列腺癌的筛查可以降低前列腺癌相关的死亡率,但对是否开展此项筛查依然存在争议。诊断方面依然以直肠指检(DRE)、前列腺特异性抗原(PSA)和B超引导的经直肠前列腺穿刺活检为主。治疗方面强调对这类患者实施治愈性治疗手段如前列腺癌根治术和放疗。严密的随访可以尽早发现肿瘤复发并及时开始二线治愈性治疗。本文对早期前列腺癌诊断与治疗的现状进行了综述。     

481例前列腺癌患者年龄与病理构成分析

目的:探讨近年来前列腺癌发病年龄和病理构成情况。方法:收集1998年1月~2004年4月经病理确诊的前列腺癌患者481例,对其年龄和病理构成进行分析。结果:1998年共有前列腺癌患者39例,1999年69例,2000年73例,2001年68例,2002年72例,2003年121例,2004年1~4月39例。患者年龄40~91岁,中位年龄72岁,95%的患者年龄为55~84岁,65岁以上患者占84.2%。病理分级中高分化14例,中分化29例,低分化83例,未进行病理分级355例。微小癌(小于1cm)40例(8.3%),偶发癌20例(4.2%)。病理类型中内膜样癌1例,鳞癌1例,印戒细胞癌1例,腺鳞癌1例,前列腺小细胞癌1例,粘液腺癌1例,腺样囊性癌1例,移行细胞癌1例,腺癌473例(98.1%)。结论:本组前列腺癌主要发生在65岁以上老年男性,病理类型绝大多数为腺癌,前列腺癌已成为危害老年男性健康的重要恶性肿瘤疾病。     

Familial Prostate Cancer in Japan

Background:
Familial prostate cancer has been studied in Europe and the United States. This study was conducted toclarify the clinical features and incidenceof the human leukocyte antigen (HLA) in familial prostate cancer in patients seen at hospitals in Japan.
Methods:
The age at diagnosis, clinical stage, histologic differentiation, prognosis, cause of death and family history were compiled from 43 patients from 20 families with familial prostate cancer (group F) and compared in patients with sporadic prostate cancer (group S). In addition, HLA class II gene typing was performed in 17 patients from 11 families with familial prostate cancer (group F') and their healthy family members (15 males and 25 females).
Results:
The age at diagnosis was significantly lower in group F patients ( P < 0.001), but neither clinical stage nor prognosis differed between group F and group S, yet the incidence of moderately differentiated adenocarcinoma was significantly higher in group F ( P & 0.01). There were no historical factors that were specific for group F patients. The frequency of HLA-DRB1 *0901 and *1201 alleles was significantly higher in group F' patients than in group J (the frequency of alleles in 1216 Japanese people attending the 11th Japan HLA Workshop), but not between group F' and their healthy male family members.
Conclusion:
There were no significant differences in clinical parameters between group F and group S, except that the age at diagnosis was lower in group F patients, and that the frequency of several HLA class II alleles was significantly higher in patients with prostate cancer. In men with a family history of prostate cancer, examinations for early detection of prostate cancer should begin at a young age.     

Managing Nonmetastatic Castration-resistant Prostate Cancer

Context

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation.