PCA3在前列腺癌患者前列腺按摩后尿液中的表达

目的检测PCA3在前列腺癌（PCa）患者前列腺按摩后尿液中的表达情况，并讨论其临床意义。方法从56例PCa患者、23例良性前列腺增生（BPH）患者和9例健康男性志愿者（对照组）前列腺按摩后初始尿液中分离细胞，采用RT—PCR方法检测其中PCA3的表达情况。结果BPH和对照组未见PCA3阳性表达，而PCa患者PCA3阳性率为81．3％（39／48），两者差异具有统计学意义（P〈0．01）。结论前列腺按摩后尿液中PCA3的检测有望成为早期诊断PCa的一种较敏感的方法，也有望成为PCa治疗后监测的一种方法。     

腹腔镜根治性前列腺切除术后切缘阳性的相关因素分析

目的：分析腹腔镜根治性前列腺切除术后切缘阳性的相关因素。方法：2004年1月～2010年12月,我院完成腹腔镜根治性前列腺切除术188例,平均年龄72岁。患者根治术前均经病理检查确诊为前列腺癌,未发现肿瘤转移征象。采用单因素分析研究各参数对切缘情况的影响,采用多因素Logistic回归分析确定切缘阳性的独立危险因素。结果：除2例患者中转开放手术外,其余患者均在腹腔镜下完成手术。平均手术时间246min,平均出血量309ml。术后病理回报切缘阳性76例,占40．5％。单因素分析提示切缘阳性组与切缘阴性组穿刺Gleason评分、穿刺阳性针数、根治病理Gleason评分、病理分期差异有统计学意义（P〈0．05）。多因素Logistic回归分析显示根治标本Gleason评分、病理分期是切缘阳性的独立相关因素。根治标本Gleason评分8分相对于Gleason评分6分患者切缘阳性风险增高17．1倍（比值比为17．131,95％置信区间为5．237～56．037,P〈0．001）,病理分期T1期相对于T2期患者切缘阳性风险增高9．0倍（比值比为8．970,95％置信区间为4．128～19．493,P〈0．001）。结论：根治标本Gleason评分、病理分期是腹腔镜根治性前列腺切除术后切缘阳性独立危险因素。根治标本Gleason评分为8分、病理分期为T3期患者的切缘阳性率显著增高。     

前列腺组织中PTTG的表达及其意义

目的：研究垂体肿瘤转化基因（PTTG）在前列腺组织,尤其是前列腺癌组织中的表达及临床意义。方法：采用免疫组织化学二步法检测正常前列腺（8例）、BPH（16例）、无远处转移的前列腺癌（47例）以及有远处转移的前列腺癌（19例）组织中PTTG的表达情况。用Stata统计软件分别对BPH和前列腺癌组织中PTTG的表达情况与PSA和Gleason分级间的关系进行分析。结果：PTTG在正常前列腺和BPH组织中无表达或弱表达,而63．7％（42／66）的前列腺癌中有阳性或强阳性表达,在良恶性前列腺组织之间的表达差异有统计学意义（x2=25．2487,P=0．000）,无远处转移的前列腺癌和有远处转移的前列腺癌之间的表达差异无统计学意义（x2=0．3568,P=0．837）。PTTG在前列腺癌中的表达与PSA和Gleason分级之间无相关性。结论：PTTG在前列腺癌组织中高表达,可能在前列腺癌的发生发展过程中起重要作用。     

组织芯片检测Claudin-3在前列腺癌中的表达

目的：检测Claudin-3在前列腺癌中的表达情况,探讨其与前列腺癌发生发展的关系。方法：采用组织芯片技术构建包含64例前列腺癌和39例前列腺增生组织的64点阵石蜡组织芯片,用免疫组化sP法检测该芯片中Claudin-3的表达,分析其与前列腺癌Gleason评分和临床分期的关系。结果：前列腺癌Claudin-3阳性表达率为60．94％（39／64）,前列腺增生表达率17．95％（7／39）（P〈0．05）;Claudin-3与前列腺癌Gleason评分和临床分期明显相关。结论：Claudin-3异常表达与前列腺癌发生发展有密切关系。     

转录因子FOXA1与前列腺癌恶性程度及进展相关性研究

目的:探讨FOXA1与前列腺癌(PCa)临床分期、组织学分级及去势抵抗性前列腺癌(CRPC)的关系。方法:收集前列腺癌患者(35例)、良性前列腺增生(BPH)患者(21例)前列腺组织病理切片,应用免疫组化方法检测FOXA1和Ki-67的表达情况,进一步分析该分子阳性表达率与肿瘤临床分期、Gleason评分和CRPC的相关性。结果:PCa患者前列腺组织中FOXA1表达率明显高于BPH患者(100%vs 71.4%,P0.01),FOXA1的表达阳性率与Ki-67表达阳性率正相关(P0.001),与CRPC无明显相关性(P=0.391),但与Gleason评分(P=0.027)和肿瘤临床分期(P=0.002)相关。结论:FOXA1在前列腺癌组织中表达阳性率增高,晚期前列腺癌最高。     

TLR4在前列腺癌中的表达及临床意义

目的：探讨TLR4在前列腺癌（PCa）中的表达情况及意义。方法：采用免疫组化法检测TLR4与Survivin蛋白在41例PCa及20例良性前列腺增生（BPH）组织中的表达,同时分析TLR4和Survivin蛋白表达与Gleason系统分级的关系。结果：TLR4与Survivin蛋白在BPH组织中的阳性表达例数分别为15例（75％）与0例（O）,在PCa组织中的阳性表达例数分别为18例（43．9％）与28例（68．3％）,TLR4表达与PCa的Gleason系统分级有显著相关性（P〈0．05）,随着Gleason评分增高,TLR4表达降低。Survivin蛋白的表达与Gleason系统分级无关（P〉O．05）。结论：TLR4表达与PCaGleason系统分级相关,其表达与PCa的发生发展密切相关,可成为估计肿瘤预后的一项指标。     

蛋白激酶Cε在前列腺癌组织中表达的临床意义

目的 探讨蛋白激酶C ε(PKCε)在不同病理类型前列腺组织中的表达及与前列腺癌病理分级、分期的关系。 方法 正常前列腺(NP)组织标本10例、前列腺增生(BPH)组织标本10例、癌旁(PC)组织标本10例、前列腺癌(PCa)组织标本43例。免疫组化法检测各组织中PKCε的表达情况,分析PKCε表达与不同病理类型及PCa分级、分期的关系。 结果 PCa组PKCε表达阳性27例,BPH组无阳性表达,NP组1例,PC组2例,差异有统计学意义(P＜0.05)。PCa组Gleason评分≥8分组中PKCε表达阳性12/13例,2～4分组4/10例,5～7分组11/20例,组间差异有统计学意义(P＜0.05)。T3期PKCε表达阳性10/12例,T4期9/10例,T1、T2期分别为1/6例和7/15例,高分期与低分期组PKCε表达差异有统计学意义(P＜0.05)。PCa转移组PKCε表达阳性9/10例,未转移组18/33例,组间差异有统计学意义(P＜0.05)。PCa患者血清PSA≤20 ng/ml者PKCε表达阳性7/15例,＞20 ng/ml组20/18例,组间差异无统计学意义(P＞0.05)。 结论 PCa组织中PKCε的表达率较高,并且与PCa病理分级、分期呈正相关,临床上可考虑作为PCa预后因子之一。     

骨桥蛋白基因在前列腺癌组织中的表达及临床意义简

目的 研究骨桥蛋白（OPN）基因在前列腺癌中的表达及临床意义。 方法 收集我院2008年1月至2011年5月行前列腺癌手术后的石蜡包埋标本80例、良性前列腺增生组织石蜡包埋标本35例。应用免疫组化MaxVision法,检测前列腺癌和前列腺增生组织中OPN的表达情况,分析 OPN的表达与临床病理参数之间的关系。结果 OPN蛋白在前列腺癌和前列腺增生组织中的阳性表达率分别为72.50%（58/80）和8.57%（3/35）, 差异具有统计学意义（P＜0.05）。OPN蛋白阳性表达率与前列腺癌的T、 M分期正相关,差异有统计学意义（P＜0.05）;OPN蛋白阳性表达率与前列腺癌的年龄、N分期和Gleason评分无相关性,差异没有统计学意义（P＞0.05）。结论 OPN蛋白在前列腺癌组织中高表达,提示OPN基因可能与前列腺癌的发生和转移过程有关。     

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。     

转甲状腺素蛋白在前列腺癌组织中的表达以及与分级分期的关系

目的 探讨转甲状腺素蛋白(TTR)在正常前列腺(NP),良性前列腺增生(BPH)以及前列腺癌组织(Pca)中的表达,以及其表达与Pca分期分级的关系.方法 收集我院10例NP、10例BPH以及52例Pca石蜡标本切片,经常规处理后,行TTR免疫组织化学研究.结果 TTR在81%(42/52例)Pca表达强阳性,而NP和BPH无表达强阳性(P<0.05);Gleason评分8～10分Pca94%(16/17例)TTR表达强阳性,Gleason评分2～4分Pca只有50%(5/10例)TTR表达强阳性(P<0.05);TTR在全部8例D期Pca表达强阳性,A期和B期只有33%(2/6例)和79%(19/24)表达强阳性(P<0.05).结论 TTR可能与Pca的发生有关,其在Pca中的表达与Pca分级及分期有关,有可能作为Pca预后的风险因子.     

基因测序筛选前列腺癌患者PCA3(DD3)基因外显子多态性

目的 筛查前列腺癌患者PCA3基因外显子单核苷酸多态性位点,初步探讨PCA3基因多态性与前列腺癌的相关性.方法 采用基因测序法对41例前列腺癌(PCa)患者和40例良性前列腺增生(BPH)患者进行PCA3基因外显子SNP位点的筛选,对筛选到的sNP位点进行前列腺癌的相关性分析.结果 PcA3基因外显子1、外显子3、外显子4区域均未检测到基因多态性位点,PCA3基因外显子2区域存在1个SNP位点(A→C),基因型分别为AA型、AC型、CC型,该位点的基冈型频率和等位基因频率与前列腺癌存在相关性(P<0.05).结论 基因测序可有效筛选到PCA3基因外显子的SNP位点,PCA3基因外显子2基因多态性可能与前列腺癌发病风险有关.     

Molecular PCA3 diagnostics on prostatic fluid

BACKGROUND: The PCA3 test on urine can improve specificity in prostate cancer (PCa) diagnosis and could prevent unnecessary prostate biopsies. In this study, we evaluated the PCA3 test on prostatic fluid and compared this with the PCA3 test on urine in a clinical research setting. METHODS: Prostatic fluid and urine samples from 67 men were collected following digital rectal examination (DRE). The sediments were analyzed using the quantitative APTIMA PCA3 test. The results were compared with prostate biopsy results. RESULTS: Using a PCA3 score of 66 as a cut-off value, the test on prostatic fluid had 65% sensitivity for the detection of PCa, 82% specificity and a negative predictive value of 82%. At a cut-off value of 43, the test on urine had 61% sensitivity, 80% specificity and a negative predictive value of 80%. CONCLUSIONS: The PCA3 test can be performed on both urine and prostatic fluid in the diagnosis of PCa with comparable results.     

Towards Early and More Specific Diagnosis of Prostate Cancer? Beyond PSA: New Biomarkers Ready for Prime Time

ContextThe current standard for early detection of prostate cancer (PCa) consists of a digital rectal examination (DRE) and a serum test for prostate-specific antigen (PSA). However, there is no definitive PSA level that can accurately differentiate men with cancer from men with benign prostatic hyperplasia. A large population of men with chronically elevated serum PSA and one or more negative prostate biopsies has now emerged who are at risk of developing clinically significant prostate cancer as they age. However, serum PSA and its derivative assays may not allow effective monitoring of these patients for PCa, and many consequently undergo repeat biopsies. While prostate biopsy remains the gold standard for PCa diagnosis, this method has its own limitations and associated comorbidities.ObjectiveMore accurate diagnostic tests are needed to help guide decisions to biopsy the prostate, and recent developments are reviewed in this paper.Evidence acquisitionPublications on prostate cancer gene 3 (PCA3) since 1999, the date the gene was described for the first time.Evidence synthesisDirect detection of cancer cells in biological fluids is attractive due to the expected improvement in specificity compared with the measurement of surrogate protein markers in blood. In addition, gene-based assays for cancer cell detection should be synergistic with immunoassays for blood antigens. PCA3 levels in urine is the first commercially available noninvasive molecular test for the diagnosis of PCa and therefore provides a case study for the successful translation of a molecular marker from the research laboratory to clinical practice.ConclusionsThis paper describes the development of PCA3-based molecular urine tests, and we also review the most recent data demonstrating the potential diagnostic and prognostic utilities of PCA3 and the initial findings of the TMPRSS2-ERG gene fusion testing.     

Contemporary role of prostate cancer antigen 3 in the management of prostate cancer

Context

Newly discovered biomarkers ideally should prove clinical usefulness, provide additional detection, staging, and prognosis information to improve individual risk assessment, and potentially permit targeted cancer therapy.

Objective

To review, display, and evaluate the current evidence regarding the biologic and analytic approach of urinary prostate cancer gene 3 (PCA3) in prostate cancer (PCa) detection, staging, and prognosis, and its therapeutic potential.

Evidence acquisition

A systematic and comprehensive Medline search was performed using the Medical Subject Headings search terms PCA3, DD3, UPM3, prostate cancer, cell-lines, prostate tissue, prostate biopsy, detection, diagnosis, radical prostatectomy, staging, grading, progression, and gene therapy. Results were restricted to English-language papers published within the period 1999-2011.

Evidence synthesis

The PCA3 gene is highly overexpressed in specific PCa cell lines and prostatic tumours. In 2006, a simple and robust urine test (Progensa) became commercially available. Despite its costs, prostate cancer antigen 3 (PCA3) is superior to prostate-specific antigen (PSA) and percent free PSA in the early detection of PCa. PCA3 improves the diagnostic accuracy of externally validated nomograms among men with an elevated PSA undergoing biopsy. PCA3 independently predicts low-volume disease and pathologically insignificant PCa but is not associated with locally advanced disease and is limited in the prediction of aggressive cancer. Preliminary data demonstrate that combining PCA3 with other new biomarkers further improves diagnostic and prognostic accuracy. Finally, findings of the first PCA3-Gene-ViroTherapy study suggest therapeutic potential by exploiting PCA3 overexpression.

Conclusions

PCA3, integrated in novel biopsy nomograms or risk stratification tools, can be used to counsel or confirm biopsy indications. If confirmed in further studies, using PCA3 together with established staging risk factors could assist clinicians in specific pretreatment decision making. So far no evidence for the usefulness of PCA3 in active surveillance programs has been presented.     

PCA3联合mMRI在前列腺癌诊断中的意义

目的探讨前列腺癌基因3（prostate cancer gene 3,PCA3）和多参数磁共振成像（multiparametric magnetic resonance imaging,mMRI）对前列腺癌的诊断意义。方法对56例首次穿刺结果为阴性但PSA持续升高的患者在第二次穿刺活检之前行PCA3和mMRI检查。评估PCA3评分和mMRI对前列腺癌诊断的准确性和可靠度及其对前列腺穿刺结果的预测性。结果 mMRI结果显示20例（35.7%）患者具有前列腺癌特征;PCA3评分（截断值为35时）显示15例（26.8%）患者疑为前列腺癌;前列腺穿刺活检结果显示23例（41.1%）患者确诊为前列腺癌。PCA3和mMRI对前列腺癌诊断的敏感性和特异性分别为67%、49%及74%、89%。结论 mMRI增加了PCA3对前列腺癌诊断的准确性和敏感性,可以减少不必要的前列腺穿刺。     

Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia

Objective

An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN.

Patients and methods

The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP).

Results

The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN.

Conclusions

The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.     

同源框基因NKX3.1在前列腺癌组织中的表达及意义

目的　探讨同源框基因NKX3.1在前列腺癌中的表达意义。　方法　采用半定量RT PCR检测前列腺癌、良性前列腺、非前列腺组织标本NKX3.1mRNA表达状况并对其扩增产物进行测序。　结果　 76例前列腺组织中 ,NKX3.1表达 75例 ,表达率 98.7%。 96例非前列腺组织标本中 ,除 2例睾丸组织、1例乳腺组织有NKX3.1表达外 ,肾、膀胱、肝、回肠、脂肪、皮肤组织无 1例表达。前列腺癌组织NKX3.1表达量明显增高 ,良性前列腺增生组织表达量明显减弱 (P <0 .0 1) ;晚期前列腺癌组织NKX3.1表达明显高于早期前列腺癌 (P <0 .0 5 ) ;低分化前列腺癌表达高于中高分化前列腺癌 (P <0 .0 5 ) ;激素依赖性前列腺癌表达高于激素非依赖性前列腺癌 (P <0 .0 1)。NKX3.1表达高低与前列腺体积和血清总PSA浓度无关 (P >0 .0 5 )。　结论　NKX3.1基因具有前列腺组织特异性 ,其表达状况与前列腺癌分期、分级相关。NKX3.1表达对于判断前列腺癌病理生物学特性和前列腺癌治疗有重要意义。     

PCNA在前列腺癌及良性前列腺增生症组织中的表达及其临床意义

目的探讨PCNA存前列腺癌及良性前列腺增生症组织中的表达及其在诊断前列腺癌的临床意义。方法运用实时荧光定量PCR方法检测40例前列腺癌病理组织以及良性前列腺增生症组织的PCNA的基冈表达水平。结果PCNA在前列腺癌组织中表达值为9．23±0．55,在良性前列腺增生症组织中表达值为1．23±0．04,前列腺癌中PCNA表达值高于良性前列腺增生症组织,差异有显著性（P〈0．01）。结论前列腺癌组织中PCNA基斟呈现为高表达,它有助于对前列腺癌的诊断。     

核干因子在前列腺癌中的表达及其临床意义

目的:探讨核干因子(NS)基因在前列腺癌组织中的表达及其临床意义。方法:利用RT-PCR及免疫组化方法对前列腺癌、良性前列腺增生(BPH)及高级别前列腺上皮内瘤(HGPIN)组织中NS基因的表达进行检测,并探讨NS蛋白表达水平与前列腺癌患者临床指标的关系。结果:前列腺癌中NSmRNA表达水平显著高于BPH中的表达水平,NS蛋白在前列腺癌中的强阳性、阳性及弱阳性表达率分别为48.8%、36.6%及12.2%,在BPH中分别为4.0%、32.0%及56.0%,在HGPIN中分别为5.0%、25.0%及60.0%,在前列腺癌中的表达水平显著高于BPH及HGPIN中的水平,具有统计学意义(P<0.05)。NS基因表达水平与前列腺癌的分化程度呈负相关,细胞分化程度越差,NS基因表达水平越高。结论:前列腺癌中高表达NS基因,NS基因在前列腺癌的不良分化和恶性增殖中可能起着重要作用。     

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。