前列腺癌组织中前列腺干细胞抗原的表达及其意义

目的 :探讨前列腺癌 (PCa)组织中前列腺干细胞抗原 (prostatestemcellantigen ,PSCA)的表达及其意义。方法 :应用核酸分子原位杂交 (ISH)技术 ,对 2 6例PCa和 9例正常前列腺 (NP)组织中PSCAmRNA进行检测和定位。结果 :PSCAmRNA在PCa组织表达阳性率为 84 .6 % ,其中强阳性率为 5 7.7% ;NP组织阳性率为6 6 .7% (均为弱阳性 )。PCa与NP组织表达水平差异有极显著性意义 (P <0 .0 1)。PSCAmRNA在PCa组织主要表达于癌细胞 ,细胞间质和肌肉组织均无表达 ;NP组织表达则定位于前列腺上皮的基底细胞层。PSCAmR NA表达水平与PCa临床分期、病理分级均无相关性 (P >0 .0 5 )。结论 :PSCA在探索PCa起源、PCa免疫靶向治疗方面有重要意义     

前列腺干细胞抗原和PTEN蛋白在前列腺癌组织中的表达及其相关性

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前列腺干细胞抗原在人前列腺癌组织中的表达及意义

目的　探讨前列腺干细胞抗原 (PSCA)在国人前列腺癌 (PCa)组织中表达的临床意义。　方法　采用免疫组织化学 (IHC)和核酸原位杂交 (ISH)方法检测 4 0例PCa、2 0例良性前列腺增生(BPH)和 2 0例前列腺上皮内瘤 (PIN)组织标本PSCA蛋白和mRNA表达 ,半定量法计算PSCA阳性表达细胞百分数和阳性表达强度 ,比较各组织间表达水平的差异及其与PCa分级、临床分期之间的关系。　结果　PCa、BPH、PIN组织PSCA中度阳性到强阳性表达分别为 85 % (34/ 4 0 )、2 0 % (4/ 2 0 )和35 % (7/ 2 0 ) ;PCa组织PSCA表达水平与BPH和PIN比较差异有统计学意义 (P <0 .0 5 ) ,BPH与PIN比较差异无统计学意义 (P >0 .0 5 ) ;PCa组织PSCA表达水平随Gleason评分及临床分期增加而升高。　结论　人PCa组织有PSCA蛋白质和mRNA的过表达 ,且与PCa病理分级、临床分期呈正相关 ,可能对PCa的诊断及判断预后有潜在价值。     

前列腺干细胞抗原（PSCA）在前列腺癌研究中的新进展

细胞表面抗原的识别对前列腺癌的诊断、治疗、预后非常关键。目前已经发现并研究了数种前列腺组织特异性蛋白，本文描述了前列腺干细胞抗原(PSCA)，一种可局限表达于前列腺的蛋白，在前列腺癌的诊断治疗中的作用。     

前列腺干细胞抗原和前列腺癌

前列腺癌 (ＰＣａ)是临床常见的恶性肿瘤之一。在美国 ,ＰＣａ是导致死亡的第二大肿瘤疾病。在中国 ,ＰＣａ的发病率也呈明显上升趋势。前列腺肿瘤标记物如ＰＡＰ、ＰＳＡ、ＰＳＭＡ等已应用于临床ＰＣａ的诊断与监测。前列腺干细胞抗原 (ＰＳＣＡ)是新近发现的一种ＰＣａ特异性标记物 ,由于它过表达于绝大部分ＰＣａ组织及骨转移灶中 ,一经发现就引起了人们对其结构、分布及其临床应用的兴趣。本文对ＰＳＣＡ的性质、结构及其与ＰＣａ的关系作一综述。1　ＰＳＣＡ的来源及结构ＰＳＣＡ基因于 1 997年由Ｒｏｂｅｒｔ等〔1〕从ＬＡＰＣ 4异种…     

PSCA应用的新进展：前列腺癌的诊断,治疗和判断预后

近几年来,随着对前列腺干细胞抗原（PSCA）研究的不断深入PSCA的应用,特别是在诊断、治疗和判断预后方面有了长足的进展。本文主要对PSCA最近在前列腺癌诊断、治疗和预后判断方面,特别是PSCA用于PET影像学诊断和最新免疫治疗方面的研究进展做一总结。     

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。     

前列腺干细胞抗原(PSCA)在前列腺癌研究中的新进展

细胞表面抗原的识别对前列腺癌的诊断、治疗、预后非常关键。目前已经发现并研究了数种前列腺组织特异性蛋白 ,本文描述了前列腺干细胞抗原 (PSCA) ,一种可局限表达于前列腺的蛋白 ,在前列腺癌的诊断治疗中的作用。     

CD147在前列腺癌组织中阳性表达与PSA失败的相关性分析

目的探讨CD147在前列腺癌组织中的表达情况及其临床意义。方法应用免疫组化S—P法检测240例前列腺癌组织中CD147的表达情况,并对CD147与前列腺癌PSA失败的关系进行统计学分析。结果CD147在无PSA失败前列腺癌组织中的阳性率为27．6％．有PSA失败的阳性率为80．7％,具有显著差异（P〈0．05）。CD147的表达与PSA失败呈正相关。结论CD147检测有助于了解前列腺癌的恶性程度,评估其预后,对临床制定治疗方案有指导意义。     

PSCA和Oct-4蛋白在肝细胞癌中的表达及其意义

目的 探讨PSCA和Oct-4蛋白在肝细胞癌(HCC)中的表达及其意义.方法 利用免疫组织化学技术检测PSCA和Oct-4蛋白在肝硬化、肝细胞癌及其癌旁肝组织中的表达.结果 结果PSCA和Oct-4蛋白阳性信号主要位于细胞质和细胞膜;HCC组织中PSCA和Oct-4蛋白的阳性率和阳性表达强度明显高于癌旁肝组织和肝硬化组织(P＜0.01);HCC中PSCA和Oct-4蛋白的阳性表达率和表达强度与其组织学分级无关.在肝硬化及癌旁肝组织中,非典型增生的肝细胞PSCA和oct-4蛋白呈强表达,且其表达率和表达强度与HCC的差异无统计学意义(P＞0.05).在肝硬化、HCC及其癌旁肝组织中,2种蛋白的表达强度呈显著正相关.结论 肝硬化及癌旁肝组织中高表达PSCA和Oct-4蛋白的细胞可能是"癌干细胞",它们主要参与HCC的发生,且两者可能具有协同作用,检测肝硬化组织中PsCA和/或oct-4蛋白的表达水平可能有助于早期发现HCC.     

前列腺特异性抗原集团普查是前列腺癌早期诊治的最佳途径

为在我国实现前列腺癌早期发现、早期诊断与治疗的目的 ,对 5 0岁以上男性进行PSA集团普查 ,以集团普查癌与临床前列腺癌进行对比分析 ,证明只有通过人群普查才能发现早期前列腺癌并为病人提供根治的机会。同时探讨了前列腺癌的治疗现状与存在的问题 ,对前列腺癌未来研究方向进行了展望     

Stem Cell Characteristics in Prostate Cancer Cell Lines

Background

Recent studies indicate the presence of a small, stem-like cell population in several human cancers that is crucial for the tumour (re)population.

Objective

Six established prostate cancer (PCa) cell lines—DU145, DuCaP, LAPC-4, 22Rv1, LNCaP, and PC-3—were examined for their stem cell properties in vitro.

Design, settings, and participants

The colony-forming efficiency and self-renewal ability of morphologically distinguishable holoclones and paraclones were tested with low-density plating and serial passaging. Expression of the putative stem cell marker CD133 and breast cancer resistance protein (BCRP) was examined with flow cytometry, and immunohistochemical stainings were made for CD133, α2-integrin, nestin, BCRP, cytokeratin 5 (CK5), and cytokeratin 18 (CK18).

Results and limitations

Five out of six cell lines formed clear holo-, mero-, and paraclones. Unlike paraclones, we can maintain DU145 holoclones in culture for several passages, which is indicative of self-renewal ability. Using fluorescence-activated cell sorting (FACS) analysis only in DU145 cells, a small fraction (0.01%) of CD133⁺ cells was detected. CD133⁺ cells; however, like DU145 BCRP⁺ (0.15%) cells, they were not more clonogenic, and they did not show more holoclone formation than the marker-negative cells or unselected cells. Immunohistochemistry revealed α2-integrin and BCRP as potential stem cell markers and CK5 with the combination of CK18 to distinguish transient amplifying cells.

Conclusions

These results indicate the possible presence of stem-like cells in several established PCa cell lines. CD133 selection does not enrich for stem-like cells in PCa cell lines.     

PSCA rs2294008基因变异对膀胱癌分级、分期的影响

目的研究 PSCA rs2294008多态性是否与膀胱癌易感性相关.方法抽取235例膀胱癌患者和200例非膀胱癌患者的血样,进行基因型测定,确定患者血样中 PSCA rs2294008基因型,进行病例对照研究.结果 rs2294008的基因型 CC、CT 和 TT 在膀胱癌患者中出现的概率分别为42．1％、47．7％、10．2％,在对照组中分别为52．0％、40．0％、8．0％;合并的 CT/TT 和 CC基因型对比,合并基因型使膀胱癌风险显著增加(CT/TT：OR＝1．37,95％CI 1．08~1．74).结论PSCA中 rs2294008的基因多态性与膀胱癌的风险相关.     

Overdiagnosis and Overtreatment of Prostate Cancer

Context

Although prostate cancer (PCa) screening reduces the incidence of advanced disease and mortality, trade-offs include overdiagnosis and resultant overtreatment.

Objective

To review primary data on PCa overdiagnosis and overtreatment.

Evidence acquisition

Electronic searches were conducted in Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception to July 2013 for original articles on PCa overdiagnosis and overtreatment. Supplemental articles were identified through hand searches.

Evidence synthesis

The lead-time and excess-incidence approaches are the main ways used to estimate overdiagnosis in epidemiological studies, with estimates varying widely. The estimated number of PCa cases needed to be diagnosed to save a life has ranged from 48 down to 5 with increasing follow-up. In clinical studies, generally lower rates of overdiagnosis have been reported based on the frequency of low-grade minimal tumors at radical prostatectomy (1.7–46.8%). Autopsy studies have reported PCa in 18.5–38.5%, although not all are low grade or low volume. Factors influencing overdiagnosis include the study population, screening protocol, and background incidence, limiting generalizability between settings. Reported rates of overtreatment vary widely in the literature, although contemporary international studies suggest increasing use of conservative management.

Conclusions

Epidemiological, clinical, and autopsy studies have been used to examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%. Correspondingly, estimates of overtreatment vary widely based on patient features and may be declining internationally. Careful patient selection for screening and reducing overtreatment are important to preserve the benefits and reduce the downstream harms of prostate-specific antigen testing. Because all of these estimates are extremely population and context specific, this must be considered when using these data to inform policy.

Patient summary

Screening reduces spread and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that may not have caused harm. Because treatment has potential side effects, it is critical that not all patients with PCa receive aggressive treatment.     

Utility of Volume Adjusted Prostate Specific Antigen Density in the Diagnosis of Prostate Cancer in Arab Men

Background: This study was undertaken to assess the utility of prostate specific antigen (PSA) and PSA density (PSAD) in discriminating between benign and malignant prostate disease in the Kuwaiti Arab population.Methods: A total of 100 consecutive patients suspected of having prostate cancer because of serum PSA > 4 ng/ml, or detection of a prostatic nodule on rectal examination were further investigated by determination of PSAD, TRUS of prostate, sexant prostatic biopsy and histological analysis to establish the correct diagnosis. Other diagnostic measures included the determination of the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. Results: Of the 100 prostate biopsies that were performed, 33 cases were confirmed to be prostate cancer and 67 were described as benign lesions comprising benign prostatic hyperplasia (BPH) with or without prostatitis. The age range for patients with prostate cancer was 42–90 years, and 52–90 years for those without prostate cancer. The mean prostate volume was 58.82 cc (range 9–177 cc) and 62.60 cc (range 15–140 cc), the mean PSA value was 36.65 ng/ml (range 5.8–200 ng/ml) and 16.49 ng/ml (range 1.4–46.0 ng/ml), while the mean PSAD was 0.92 (range 0.046–5.714) and 0.452 (range 0.034–2.294) for patients with prostate cancer and patients without prostate cancer respectively. Patients with PSA less than 4 ng/ml (3 cases) all had benign prostate lesions, and 7 cases with PSA more than 50 ng/ml all had prostate cancer and were excluded because values above 50 ng/ml have close to 100% specificity for prostate cancer. Further analysis was done on the remaining 90 cases which were patients with a PSA between 4 and 50 ng/ml. The discriminating power of serum PSA for detecting prostate cancer as estimated by the area under ROC was 0.686 while that for PSAD was 0.732. The maximum likelihood for a positive PSA was at a PSAD cut-off point of 0.32. For the PSA cut-off point of l0 ng/ml, the sensitivity was 80%, and specificity was 42.2%. For the PSAD cut-off point of 0.32, the sensitivity was 58% and the specificity 76.6%. Conclusions: Determination of PSAD is not a useful adjunct to serum PSA values in the range of 10–50 ng/ ml in our population. PSAD value less than 0.32 with PSA less than l0 ng/ml strongly suggests benign disease.     

Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates

ContextPrevious studies have reported significant variation in prostate cancer rates and trends mainly due to differences in detection practices, availability of treatment, and underlying genetic susceptibility.ObjectiveTo assess recent worldwide prostate cancer incidence, mortality rates, and trends using up-to-date incidence and mortality data.Evidence acquisitionWe present estimated age-standardized prostate cancer incidence and mortality rates by country and world regions for 2018 based on the GLOBOCAN database. We also examined rates and temporal trends for incidence (44 countries) and mortality (76 countries) based on data series from population-based registries.Evidence synthesisThe highest estimated incidence rates were found in Australia/New Zealand, Northern America, Western and Northern Europe, and the Caribbean, and the lowest rates were found in South-Central Asia, Northern Africa, and South-Eastern and Eastern Asia. The highest estimated mortality rates were found in the Caribbean (Barbados, Trinidad and Tobago, and Cuba), sub-Saharan Africa (South Africa), parts of former Soviet Union (Lithuania, Estonia, and Latvia), whereas the lowest rates were found in Asia (Thailand and Turkmenistan). Prostate cancer incidence rates during the most recent 5 yr declined (five countries) or stabilized (35 countries), after increasing for many years; in contrast, rates continued to increase for four countries in Eastern Europe and Asia. During the most recent 5 data years, mortality rates among the 76 countries examined increased (three countries), remained stable (59 countries), or decreased (14 countries).ConclusionsAs evident from available data, prostate cancer incidence and mortality rates have been on the decline or have stabilized recently in many countries, with decreases more pronounced in high-income countries. These trends may reflect a decline in prostate-specific antigen testing (incidence) and improvements in treatment (mortality).Patient summaryWe examined recent trends in prostate cancer incidence and mortality rates in 44 and 76 countries, respectively, and found that rates in most countries stabilized or decreased.     

Prostate stem cell antigen (PSCA) mRNA expression in prostatic intraepithelial neoplasia: implications for the development of prostate cancer

BACKGROUND: Prior data clearly demonstrated the expression of prostate stem cell antigen (PSCA) mRNA in prostatic intraepithelial neoplasia (PIN) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression was associated with the presence of cancer in this disease. METHODS: One hundred seventeen men were diagnosed with isolated PIN on initial prostate biopsy, 51 with low-grade form (LGPIN), and 66 with high-grade form (HGPIN). PSCA mRNA expression in initial PIN and subsequent cancer was examined by in situ hybridization (ISH). The differences of the PSCA mRNA expression level between the groups were analyzed by the Chi-square and Student's t-test. Univariate and multivariate logistic regression analyses were performed to evaluate the predictive performance of PSCA mRNA. RESULTS: PSCA mRNA expression level in 34 subsequent cancers was statistically increased compared with their paired PIN (P < 0.001), with a Gleason's dependence. HGPIN showed statistically high PSCA mRNA expression compared with LGPIN (P < 0.01). PSCA mRNA expression levels were significantly stronger in the initial isolated LGPIN and isolated HGPIN with subsequent cancer than those without (P < 0.001 and P < 0.001, respectively). Multivariate logistic regression analysis demonstrated that only PSCA mRNA was predictive of the onset of subsequent cancer in patients with isolated LGPIN and in those with isolated HGPIN, respectively. CONCLUSIONS: Our data identify PSCA mRNA in initial PIN as a significant predictor of subsequent cancer, suggesting that PSCA implies in prostatic tumorigenesis and may be used to identify the patients with isolated PIN who are at high risk for cancer onset in the disease process.     

Cerebrospinal Fluid Prostate Specific Antigen (CSF PSA) in Prostate Cancer Patients with Lower Spine Metastasis

Aim: In this prospective study, our aim was to investigate the CSF PSA levels and CSF/Serum PSA ratios in patients with prostate cancer with lower spine metastasis. Methods: The study involved patients with prostate cancer (n = 15), benign prostatic hyperplasia (n = 17) and non-prostatic disease (n = 9). Serum and CSF were obtained prior to spinal anesthesia for urological surgery. Total PSA levels in the serum and CSF were measured by electrochemiluminescence immunoassay. The results were tested statistically using the Mann–Whitney U test. Results: The mean serum PSA levels were 20.36 ng/ml in the prostate cancer patients, 5.37 ng/ml in the BPH patients and 0.76 ng/ml non-prostatic disease. The mean CSF PSA levels in groups were 0.127, 0.051 and 0.027 ng/ml, respectively. The mean CSF PSA/serum PSA ratios in groups were 0.007, 0.018 and 0.042, respectively. This result is statistically significant (P < 0.001).Conclusions: Although mean serum PSA and CSF PSA levels in the patients with cancer of the prostate and lower spine metastasis are higher than those in the others, the mean CSF PSA/serum PSA ratio is lower. However, clinical usefulness of CSF PSA value and CSF PSA/ Serum PSA ratio can be limited because CSF PSA values are usually very low, and CSF PSA/Serum PSA ratio of 4 prostate cancer patients are as high as 1 BPH patient.