PCA3 mRNA与PSA mRNA的联合检测对前列腺癌早期诊断的临床意义

目的评价外周血前列腺癌抗原基因-3（prostate cancer antigen3,PCA3 mRNA）和前列腺特异性抗原基因（prostate specific antigen,PSA mRNA）联合检测对前列腺癌（PCa）早期诊断的价值,及决定是否进行前列腺穿刺活检。方法纳入41例PCa和69例前列腺增生（BPH）患者的外周血,采用RT—PCR方法对其PCA3mRNA和PSAmRNA进行检测,通过受试者工作特征（ROC）曲线评价其在预测前列腺穿刺活检结果和PCa早期诊断的价值。结果PCa组外周血PCA3mRNA含量明显高于BPH组[2362（〈30～7421）拷贝／ml比〈35拷贝／ml,z=-6．66,P〈0．01],而PSAmRNA含量也明显高于BPH组[3425（908～36639）拷贝／ml比〈220拷贝／ml,z=-6．40,P〈0．01];ROC曲线显示当PCA3mRNA和PSAmRNA临界值分别为846拷贝／ml和280拷贝／ml时,诊断早期PCa结果为73．2％（30／41）、85．4％（35／41）,特异度分别为87．0％（60／69）、78．3％（54／69）;而联合检测时其敏感度可增至90．2％（37／41）,特异度上升为89．9％（62／69）。结论外周血PCA3mRNA和PSAmRNA检测都是PCa诊断的良好指标,而它们的联合检测可弥补PCA3mRNA敏感性低和PSAmRNA特异性低的缺点,更有利于早期PCa诊断。     

前列腺癌患者PCA3 mRNA的表达及其临床意义

目的：评价PCA3在前列腺癌诊断、临床分期及Gleason评分中的临床应用价值。方法：选取2005年11月～2006年9月在我院住院的前列腺癌患者56例，其中T2期12例，T3期21例，T4（N0～3，M0～1）期23例；Gleason评分5～7分27例，8～10分29例；BPH患者23例，健康男性9例。分别获取其外周血及前列腺按摩液，采用RT—PCR方法检测两种体液标本中PCA3的表达阳性情况，使用SPSS12．0统计软件包对其结果进行分析。结果：BPH和对照组两种体液标本未见PCA3阳性表达，而PCa患者外周血标本PCA3阳性率为88．9％（48／54），前列腺按摩液标本PCA3阳性率为81．3%（39／48），差异均有统计学意义（P〈0．01）。结论：两种体液标本PCA3的阳性表达有明显的前列腺癌特异性，并且随着前列腺癌的临床分期增高，其阳性率越高，有望成为诊断前列腺癌的新肿瘤标志物和判断预后的指标。     

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。     

血清EPCA-2检测在前列腺癌诊断中的临床意义

目的：通过比较血清中早期前列腺癌抗原-2（EPCA-2）与前列腺特异性抗原（PSA）在前列腺癌（PCa）诊断中的特异性与敏感性,研究血清中EPCA-2对诊断PCa的临床意义。方法：收集非前列腺疾病患者20例（作为A组）,BPH患者56例（作为B组）,PCa患者44例（作为C组）,采用酶联免疫吸附实验（ELISA）分别检测三组患者血清中EPCA-2和PSA水平,进行统计学分析。结果：①C组患者血清中EPCA-2和PSA水平分别与A组和B组患者的进行比较,均显著增高,差异有统计学意义（P〈0．01）。②A组血清中EPCA-2水平均≤分界点（30μg／L）。③以30μg／L为分界点,EPCA-2对PCa诊断的特异性为92．1％,敏感性为93．2％;以4μg／L为分界点,PSA对PCa诊断的特异性为55．3％,敏感性为79．5％;PSA结合fPSA／tPSA（以0．15为分界点）,对PCa诊断的特异性为78．9％,敏感性为68．2％。结论：EPCA-2作为新的诊断PCa的肿瘤标志物,较PSA具有更高的特异性和敏感性,对临床PCa的诊断具有重要意义。     

ROC曲线分析比较tPSA、fPSA／tPSA和PSAD在PSA灰区前列腺癌诊断中的价值

目的 ROC曲线分析探讨前列腺特异性抗原密度(PSAD)、总PSA(tPSA)和游离PSA/总PSA(fPSA/tPSA)3者在PSA灰区前列腺癌(PCa)中的临床诊断价值.方法 同顾性分析tPSA在4～10ng/ml之间的前列腺增生(BPH)患者75例和前列腺癌患者31例.化学发光法测定血清tPSA和fPSA,经直肠超声(TRUS)测定前列腺体积,计算fPSA/tPSA和PSAD.比较BPH组和PCa组间tPSA、PSAD和fPSA/tPSA各指标的差异,分析各指标在ROC曲线卜的面积、各指标的诊断特异性及敏感性.结果 PCa组与BPH组tPSA差异无统计学意义(P＞0.05),PCa组fPSA/tPSA比值较BPH组降低(P＜0.01),PSAD值较BPH组升高(P＜0.05).ROC曲线下的面积从大到小为fPSA/tPSA＞PSAD＞tPSA.在诊断敏感性相同的情况下,fPSA/tPSA比值诊断特异性高于PSAD的诊断特异性.当fPSA/tPSA临界值取0.16时,诊断前列腺癌的灵敏度和特异性为67.7%和79.7%,PSAD临界值取0.12时,其灵敏度和特异性为61.3%和62.7%.结论 当tPSA在诊断灰区时,PSAD和fPSA/tPSA可以提高前列腺癌的诊断特异性和敏感性,fPSA/tPSA较PSAD有更高的诊断价值.     

尿沉渣PSGR检测在前列腺首次穿刺患者中的诊断作用

目的:探讨尿沉渣PSGR评分在前列腺癌患者中的诊断作用。方法:2010年1月~2013年10月收集299例在我院行前列腺穿刺患者前列腺按摩后尿液,应用实时定量PCR检测尿沉渣中PSGR mRNA和PSA mRNA的表达。PSGR评分使用PSGR mRNA/PSA mRNA×1 000计算;PSGR评分的预测作用使用ROC曲线分析并与血清PSA进行比较。结果:可分析样本比例为81.94%(245/299)。所有患者和PSA"灰区"患者前列腺穿刺阳性率分别为33.46%(83/245)和27.05%(33/122)。前列腺穿刺阳性患者PSGR评分明显高于前列腺穿刺阴性患者(P0.001)。经ROC曲线分析,在所有患者中,血清tPSA、PSGR评分和两者合用的曲线下面积分别为0.584、0.687和0.713。PSGR评分与血清总PSA诊断价值比较差异无统计学意义(P=0.052),但两者合用优于单用血清tPSA(P=0.002)。当处于PSA"灰区"时,血清tPSA、PSGR评分和两者合用的曲线下面积分别为0.525、0.727和0.731。PSGR评分的诊断价值明显优于血清tPSA(P=0.004)。结论:PSGR评分在前列腺穿刺患者中有良好的预测作用,血清tPSA和PSGR评分联合应用可提高预测总体患者的准确性,单用PSGR评分对PSA"灰区"患者有较好的预测作用。     

上海闵行区PSA异常的老年男性前列腺疾病跟踪调查与分析

目的 :了解老年男性前列腺疾病的发病情况及前列腺特异抗原 (PSA)、游离PSA(fPSA)、fPSA与血清总PSA(tPSA)的比值 (f/t)跟年龄、前列腺体积 (PV)之间的关系。方法 :对 142 5名老年男性进行前列腺指检 (DRE)和PSA测定 ,然后对其中tPSA >4μg/L者进行了随访复查 ,检查项目包括DRE、tPSA、fPSA和经直肠前列腺B超 ,并建议行前列腺穿刺活检。结果 :142 5例调查者中 ,tPSA >4μg/L者 16 9例 (11.9%) ,其中 84例得到随访 ,发现tPSA、f/t与年龄无相关性 (P >0 .0 5 ) ,而PV与年龄呈正相关 (P <0 .0 5 )。 17例接受了前列腺穿刺活检 ,1例接受手术治疗 ,其中 9例被病理检查证实为前列腺增生 (BPH) ,9例被证实为前列腺癌 (PCa)。BPH组与PCa组tPSA差异有显著性意义 ,而两组PV差异无显著性意义。结论 :PSA是诊断前列腺癌的重要瘤标 ,前列腺“6点法”穿刺活检是诊断前列腺癌有效而必要的方法。     

诊断性前列腺电切术对血清PSA异常患者的应用研究

目的:探讨诊断性前列腺电切(TURP)在前列腺增生合并血清PSA异常患者中的应用价值及意义,为临床处理前列腺增生合并血清PSA异常的患者提供一种新的手段。方法:收集符合入组标准的患者71例,总结病理为前列腺癌患者的Gleason评分及预后。对所有患者进行术后随访,检测其TURP术后6个月、1年的PSA值及IPSS评分,分析术后血清PSA值、IPSS的变化,评估TURP在前列腺增生伴血清PSA异常患者中的诊疗效果。结果:①40例前列腺穿刺活检阴性而血清PSA持续异常的患者中,2例术后病理示前列腺腺癌(2/40),Gleason评分为6分,另1例电切后病理示前列腺增生组织,但术后血清PSA持续异常(18μg/L),行2次活检,病理诊断为前列腺癌,Gleason评分6分,3例均行前列腺根治性切除术,术后随访恢复好。31例拒绝活检患者中术后病理示前列腺腺癌9例(9/31)。Gleason评分7⁹分,平均8分,1例行前列腺根治性切除术,8例行内分泌治疗。②59例病理诊断为良性前列腺增生(BPH),其中血清PSA恢复正常者56例,显著降低者3例,IPSS评分有明显改善53例,6例尿道狭窄经过尿扩处理后评分亦有改善。结论:诊断性TURP可提高前列腺癌的早期检出率,改善患者的下尿路症状,且有利于患者血清PSA持续正常化。对血清PSA异常(>4μg/L),伴有下尿路梗阻状态、前列腺穿刺活检阴性的患者可考虑行诊断性TURP。     

DD3和PSA基因在前列腺癌组织中的定量表达分析

目的探讨DD3 mRNA和PSA mRNA在前列腺组织中表达的临床意义及诊断前列腺癌(PCa)的价值。方法荧光定量RT—PCR法分析21例PCa组织、39例良性前列腺增生(BPH)组织DD3 mRNA和PSA mRNA的表达,ROC曲线对DD3 mRNA、PSA mRNA和DD3 mRNA／PSA mRNA比值诊断PCa的价值进行分析。结果PCa组织中DD3 mRNA、PSA mRNA表达量和DD3 mRNA／PSA mRNA比值均显著高于BPH组织,差异有统计学意义(P<0．01)。不同临床分期和分化程度之间DD3 mRNA、PSA mRNA和DD3 mRNA／PSA mRNA比值差异无统计学意义(P值均>0．05)。ROC曲线分析结果显示,DD3 mRNA、PSA mRNA和DD3 mRNA／PSA mRNA的曲线下面积分别为0．937、0．755和0．839。当DD3 mRNA、PSA mRNA和DD3 mRNA／PSA mRNA临界值分别为1．4×105拷贝／mg组织、3．0×107拷贝／mg组织和5．0×10-3时,敏感性分别为90．5％、81．0％和81．0％,特异性分别为85．0％、62．0％和66．7％。若将DD3 mRNA和PSA mRNA联合用于PCa的诊断,其特异性与DD3 mRNA相同,为85．0％,敏感性可达100．0％。结论PCa组织中DD3 mRNA和PSA mRNA表达量均增加,但组织中DD3 mRNA的定量检测更具诊断价值,联合检测有利于提高诊断敏感性,对PCa的诊断具有一定临床应用价值。     

uPCA3mRNA及PCA3mRNA/D定量检测对PSA灰区前列腺癌诊断的临床研究

目的:研究前列腺按摩后尿液中PCA3mRNA及PCA3mRNA密度的定量检测在前列腺特异性抗原(PSA)灰区前列腺癌(PCa)临床诊断中的应用价值。方法:选择sPSA在4~10ng/ml的BPH或PCa患者200例,收集其前列腺按摩后尿液,离心取细胞沉淀物,提取总RNA,用实时荧光定量RT-PCR方法检测PSAmRNA、PCA3mRNA的含量,以PSAmRNA来校正尿液中的前列腺癌细胞。以PCA3mRNA/PSAmRNA表示PCA3mRNA的含量,经直肠B超测定前列腺体积,计算PSAD和PCA3mRNA密度(PCA3mRNA/D)。以穿刺活检或术后病理检查结果为金标准,用ROC曲线对PCA3mRNA及PCA3mRNA/D诊断PSA灰区PCa的性能进行评价。结果:PCa组的tPSA、PSAD均较BPH组升高(P0.05或0.01)。PCa组PCA3mRNA(P=0.009)含量及PCA3mRNA/D比值(P=0.005)均高于BPH组;以2.01为截断值时,尿PCA3mRNA/D比值诊断PCa的ROC曲线下面积(AUC)为0.903(95%CI:0.790~0.869),其诊断PCa的敏感度和特异度分别为93.3%和66.7%。尿PCA3mRNA/PSAmRNA比值诊断PCa的ROC曲线下面积(AUC)为0.841(95%CI:0.666~0.997),以0.27为截断值时,其诊断PCa的敏感度和特异度为86.5%和77.5%。结论:PCA3mRNA含量和PCA3mRNA/D两个指标定量检测,可以显著提高检出PSA灰区PCa的敏感度,可用于早期PCa的诊断。其中PCA3mRNA/D具有更好的诊断效能。     

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。     

Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy

Background

The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy.

Objective

This study evaluated the clinical utility of the PROGENSA PCA3 assay.

Design, setting, and participants

This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy.

Measurements

After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA).

Results and limitations

In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score ≥7 versus <7, and “significant” versus “indolent” (clinical stage T1c, PSA density [PSAD] <0.15 ng/ml, Gleason score in biopsy ≤6, and percent positive cores ≤33%) pCA.

Conclusions

The probability of a positive repeat biopsy increases with rising PCA3 scores. The PCA3 score was superior to %fPSA for predicting repeat prostate biopsy outcome and may be indicative of clinical stage and significance of pCa.     

The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Prior studies have shown that the PCA3 Score is indicative of prostate cancer significance and may aid in selecting men with clinically insignificant prostate cancer who could be candidates for active surveillance. This analysis of data from two studies enrolling 1,009 men shows that the PCA3 Score is associated with many biopsy and pathological features of the insignificant prostate cancer. The paper also provides guidance for the use of the PAC3 Assay in clinical practice.

OBJECTIVE

• ? To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance.

PATIENTS AND METHODS

• ? Clinical data from two multi‐centre European open‐label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed.
• ? First‐catch urine was collected after digital rectal examination (three strokes per lobe) and the PCA3 score was determined using the PROGENSA® PCA3 assay.
• ? Transrectal ultrasound‐guided biopsy (≥8 cores) and radical prostatectomy (RP) specimens were analysed by the local pathologist. The relationship between biopsy and RP outcomes with the PCA3 score was assessed.

RESULTS

• ? Of the 1009 men enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were statistically significantly lower in men with biopsy Gleason score <7 vs ≥7, with clinical stage T1c vs T2a–T2c, T3a cancers, with ≤33% vs >33% positive biopsy cores and with ‘biopsy indolent’ vs ‘biopsy significant’ prostate cancer (indolent prostate cancer defined by biopsy Epstein criteria).
• ? In all, 175 men with a positive biopsy had a RP: median and mean PCA3 scores were statistically significantly lower in men with pathological Gleason score <7 vs ≥7, and with pathological stage T2a–T2c vs T3a–T3b cancers.

CONCLUSIONS

• ? The PCA3 score may combined with traditional tools aid in identifying men with clinically insignificant prostate cancer, as shown by biopsy and RP pathological features including biopsy Epstein criteria, who could be candidates for active surveillance.
• ? Treatment selection should be based on a combination of clinical and pathological variables. If one wants to use a threshold point to guide treatment decisions in clinical practice, a PCA3 score threshold of 20 may have the highest utility for selecting men with clinically insignificant prostate cancer in whom active surveillance may be appropriate; a PCA3 score threshold of 50 may be used to identify men at high risk of harbouring significant prostate cancer who are candidates for RP.
• ? Although the association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management strategies may provide clinicians with another tool to more accurately determine the course of treatment.