前列腺特异膜抗原对前列腺疾病的临床诊断意义

目的评价血清中前列腺特异膜抗原（PSMA）浓度对前列腺疾病的辅助诊断意义。方法采用Western印迹分析检测患者血清中PSMA的浓度,前列腺特异抗原（PSA）检测采用通用的免疫化学发光法检测。分析二者在不同分组中的浓度差异及相关性。结果前列腺癌患者的血清中PSMA浓度显著高于正常人群,良性前列腺增生和前列腺炎的患者则低于正常人群,而PSA浓度无论是前列腺癌还是前列腺良性病变均高于正常人。结论前列腺特异膜抗原浓度可以作为区分前列腺癌和良性前列腺增生的辅助诊断标志物。     

前列腺特异性膜抗原在前列腺癌患者外周血和组织中的表达及意义

目的探讨前列腺特异性膜抗原（PSMA）在前列腺癌患者（PCa）外周血和组织中的表达及其与肿瘤病理分级和临床分期之间的关系。方法采用RT-PCR方法检测前列腺特异性膜抗原（PSMA）在前列腺癌和良性增生患者外周血清中的表达;采用免疫组化法观察PSMA在前列腺不同病变组织中的表达。前列腺癌28例,前列腺上皮内瘤（PIN）7例,良性前列腺增生（BPH）30例。结果血清学检测显示PSMA mRNA在前列腺癌和良性病变组（包括PIN和BPH）患者外周血中阳性率分别为67.9%和8.1%,两者差异具有显著性（P〈0.01）。在局限性癌、局部进展性癌和远处转移癌患者外周血肿瘤细胞中,PSMA mRNA的阳性率分别为58.3%、66.7%和85.7%,随前列腺癌临床分期的进展而逐渐递增（P〈0.05）。在高分化、中分化和低分化前列腺癌中,PSMA mRNA的阳性率分别为87.5%、62.5%和50%,肿瘤分化越差,其阳性率越低（P〈0.05）。组织学检测显示PSMA在PCa、PIN、BPH三种不同前列腺病变组织中的阳性率分别为60.7%、28.6%和20.0%（P〈0.05）,在高、中、低分化前列腺癌组织中PSMA的阳性率分别为100.0%、50.0%和25.0%,与肿瘤Gleason评分之间呈负相关（P〈0.05）。在局限性癌、局部进展性癌和远处转移癌患者肿瘤组织中,PSMA的阳性率分别为58.3%（7/12）、77.8%（7/9）和42.9%（3/7）（P〉0.05）。结论PSMA在前列腺癌组织中明显高表达,并且表达量与前列腺癌临床分期和分化程度（组织学分级）密切相关;检测PSMA可能对前列腺癌诊断、治疗方案的选择及预后评估具有重要价值。     

前列腺特异性抗原人类激肽释放酶2和前列腺特异的膜抗原在前列腺癌患者外周血表达的临床意义

目的　探讨检测前列腺癌微转移的灵敏和特异性指标。方法　从 5 1例前列腺癌、33例前列腺增生 (BPH)患者及 32名正常人的外周血中分离单个核细胞 ,用巢式RT PCR方法检测其中前列腺上皮细胞前列腺特异性抗原 (PSA)、人类激肽释放酶 2 (hK2 )和前列腺特异的膜抗原 (PSMA)的表达。结果　PSA、hK2和PSMA在前列腺癌患者外周血中检出的阳性率分别为 5 2 .9%、4 3.1%和6 4 .7% ;正常人和BPH患者假阳性率分别为 6 .2 %、7.7%和 4 .6 % ,3项指标差异均有显著性 (P <0 .0 1)。各临床分期 (局限癌、侵袭性癌和转移癌 )间 ,PSA和hK2的阳性检出率差异无显著性 ;PSMA在各期前列腺癌中阳性检出率均较PSA和hK2高 ,且随临床分期进展 ,其阳性检出率亦增加 (P <0 .0 5 )。结论PSMA对前列腺癌诊断、治疗方案的选择及预后评估较PSA和hK2有更大的价值     

Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues: implications for prostate carcinogenesis and progression of prostate cancer

OBJECTIVE: Prostate stem cell antigen (PSCA) is a recently defined homolog of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. The objective of the present study was to examine the expression status of PSCA protein and mRNA in clinical specimens of human prostate cancer (PCa) and to validate it as a potential molecular target for diagnosis and treatment of PCa. METHODS: Immunohistochemical (IHC) and in situ hybridization (ISH) analyses of PSCA expression were simultaneously performed on paraffin-embedded sections of 20 benign prostatic hyperplasia (BPH), 20 prostatic intraepithelial neoplasm (PIN) and 48 prostate cancer (PCa) tissues, including 9 androgen-independent prostate cancers. The level of PSCA expression was semiquantitatively scored by assessing both the percentage and intensity of PSCA-positive staining cells in the specimens. We then compared the PSCA expression between BPH, PIN and PCa tissues and analyzed the correlations of PSCA expression level with pathological grade, clinical stage and progression to androgen-independence in PCa. RESULTS: In BPH and low grade PIN, PSCA protein and mRNA staining were weak or negative and less intense and uniform than that observed in high grade PIN (HGPIN) and PCa. Moderate to strong PSCA protein and mRNA expression were noted in 8 of 11 (72.7%) HGPIN and in 40 of 48 (83.4%) PCa specimens examined by IHC and ISH analyses, and their statistical significance was compared with BPH (20%) and low-grade PIN (22.2%) specimens (P < 0.05). The expression level of PSCA increased with a higher Gleason grade, advanced stage and progression to androgen-independence (P < 0.05). In addition, IHC and ISH staining revealed a high degree of correlation between PSCA protein and mRNA overexpression. CONCLUSIONS: Our data demonstrate that PSCA as a new cell surface marker is overexpressed in a majority of cases of human PCa. PSCA expression correlates positively with adverse tumor characteristics, such as increasing pathological grade (poor cell differentiation), worsening clinical stage and androgen-independence and speculatively with prostate carcinogenesis. PSCA may possess prognostic utility and may be a promising molecular target for diagnosis and treatment of PCa.     

PSAD和游离/总PSA比值在前列腺癌诊断中的意义

 目的　比较研究前列腺特异抗原(PSA)、PSA密度(PSAD)和游离/总PSA比值(F/TPSA)在前列腺癌诊断中的价值。方法　41例前列腺增生和22例前列腺癌患者,术前用放免法测定血清PSA和游离PSA。所有患者经直肠腔内B超测出前列腺体积,求得PSAD,用t检验比较分析。结果　前列腺癌组的PSA、PSAD均显著高于前列腺增生组(PSA：46.3±33.8μg/Lvs7.04±6.91μg/L,P=0.000021;PSAD：1.43±1.21μg。L-1。ml-1vs0.14±0.15ng。ml-1。ml-1,P=0.000055)。两组的F/TPSA比值无显著差异(0.18±0.11vs0.22±0.18,P=0.34)。结果　PSA和PSAD是鉴别前列腺癌的良好指标,对于PSA可疑者,PSAD有助于区分前列腺癌和前列腺增生,本组游离/总PSA比值不能帮助鉴别诊断。     

Prostate Specific Antigen,Mean Platelet Volume,and Platelet Distribution Width in Combination to Discriminate Prostate Cancer from Benign Prostate Hyperplasia

Background: Prostate cancer (PCa) represents the second most commonly diagnosed malignancy and the sixthleading cause for cancer related death among men worldwide. Although use of the prostate specific antigen (PSA) asa diagnostic marker has improved the detection and management of PCa, low specificity and sensitivity has limited itsclinical efficacy. Moreover, elevated PSA is frequently observed in benign prostate hyperplasia (BPH). Mean plateletvolume (MPV) and platelet distribution width (PDW) are commonly used indicators of platelet activation. The purposeof current study was to investigate the ability of PSA, MPV, and PDW individually or in combination, to differentiatePCa from BPH. Materials and Methods: This study included 100 patients with PCa and 108 patients with BPH. Wecollected all participants’ clinical and laboratory characteristics. The benefit of adding MPV and PDW to a modelwith only PSA was evaluated as an increased in the area under the curve (AUC) obtained by receiver operating curve(ROC). Results: PCa patients had reduced MPV and elevated PSA and PDW levels compared to BPH patients. Singlebiomarkers had AUC values ranging from 0.683 for PDW to 0.865 for PSA. Moreover, the combination of PSA, MPV,and PDW increased the AUC to 0.935 (0.892-0.964) (p<0.0001), significantly higher than those of any single marker.Conclusions: The combined use of PSA, MPV, and PDW may be clinically useful in distinguishing between PCa andBPH.     

Frequency of PSA-mRNA-bearing cells in the peripheral blood of patients after prostate biopsy

Transrectal ultrasound (TRUS) guided prostate biopsy is standard diagnostic procedure for prostate cancer (PCa). However, possibility of dissemination of cancer cells by biopsy is not negligible. To investigate this possibility, we examined prostate specific antigen (PSA)-bearing cells in peripheral blood of the 108 patients before and after prostate biopsy. Peripheral blood samples were obtained from 108 patients with elevated serum PSA (sPSA) levels, who had undergone sextant prostate biopsy using TRUS. The presence of PSA-mRNA bearing cells was examined using the nested RT-PCR method enabling detection of one LNCaP cell diluted in 1 ml of whole blood. Among 108 patients, 62 and 46 were diagnosed with benign prostatic hyperplasia (BPH) and PCa, respectively. PSA-mRNA was detected in 3 PCa cases but in no BPH patients before and after biopsy, and in 16 BPH (25.8%) and in 21 PCa (45.7%) patients only after biopsy (P< 0.01). The patients with positive mRNA before biopsy had higher sPSA (P< 0.001), and those after biopsy had higher sPSA and PSA density (PSAD) levels (P< 0.05). Positive PSA-mRNA cases had more cancer involved biopsy cores than the negative PSA-mRNA cases (P< 0.001). Although further investigations are needed, the present findings suggest that prostate biopsy might scatter prostate cells in the blood stream especially in cases with high sPSA and, thus, might contribute to tumour spreading in the cases of prostate cancer.     

A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4-10 ng/ml it has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). PSA in serum is comprised of a variety of both "free" and "complexed" forms that have been used to improve the specificity of PSA for prostate cancer detection. We previously reported that pro PSA (pPSA), the zymogen or precursor form of PSA, is a component of free PSA in the serum of PCa patients. In the current study, we examined prostate tissues to understand the origin and specificity of pPSA. PSA was immuno-affinity purified from matched sets of prostate tissues including peripheral zone cancer (PZ-C); peripheral zone noncancer; and benign tissue from the transition zone (TZ), the primary site of BPH within the prostate. We found that pPSA is differentially elevated in PZ-C, but is largely undetectable in TZ. N-terminal sequencing revealed that the pPSA was comprised primarily of [-2]pPSA and minor levels of [-4]pPSA, containing pro leader peptides of 2 and 4 amino acids, respectively. The median value of pPSA was 3% in PZ-C and 0% (undetectable) in TZ (P < 0.0026). No pPSA was detected in 13 of 18 transition zone specimens (72%), but only 2 of the 18 matched cancer specimens (11%) contained no measurable pPSA. These results demonstrate that pPSA is more highly correlated with prostate cancer than with BPH. The pPSA in serum may represent a more cancer-specific form of PSA that could help distinguish prostate cancer from BPH.     

Predictive Value of the Platelet-To-Lymphocyte Ratio in Diagnosis of Prostate Cancer

Purpose: To predict prostatic carcinoma using a logistic regression model on prebiopsy peripheral bloodsamples. Materials and Methods: Data of a total of 873 patients who consulted Urology Outpatient Clinics of FatihSultan Mehmet Training and Research Hospital between February 2008 and April 2014 scheduled for prostatebiopsy were screened retrospectively. PSA levels, prostate volumes, prebiopsy whole blood cell counts, neutrophiland platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), biopsy resultsand Gleason scores in patients who had established diagnosis of prostate cancer (PCa) were evaluated. Results:This study was performed on a total of 873 cases, with an age range 48-76 years, divided into three groups asfor biopsy results. with diagnoses of benign prostatic hyperplasia (BPH) (n=304, 34.8 %), PCa (n=265, 30.4 %)and histological prostatitis (n=304; 34.8 %). Intra- and intergroup comparative evaluations were performed.White blood cell and neutrophil counts in the histological prostatitis group were significantly higher than thoseof the BPH and PCa groups (p=0.001; p=0.004; p<0.01). A statistically significant intergroup difference wasfound for PLR (p=0.041; p<0.05) but not lymphocyte count (p>0.05). According to pairwise comparisons, PLRwere significantly higher in the PCa group relative to BPH group (p=0.018, p<0.05, respectively). Though notstatistically significant, higher PLR in cases with PCa in comparison with the prostatitis group was remarkable(p=0.067, and p>0.05, respectively). Conclusions: Meta-analyses showed that in patients with PSA levels over4 ng/ml, positive predictive value of PSA is only 25 percent. Therefore, novel markers which can both detectclinically significant prostate cancer, and also prevent unnecessary biopsies are needed. Relevant to this issuein addition to PSA density, velocity, and PCA3, various markers have been analyzed. In the present study, PLRw ere found to be the additional predictor of prostatic carcinoma.     

Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and 1 BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and 11 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for delta-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer.     

Molecular forms of prostate‐specific antigen in serum with concentrations of total prostate‐specific antigen <4 μg/L: Are they useful tools for early detection and screening of prostate cancer?

Molecular forms of prostate-specific antigen (PSA) improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) in men with total PSA concentrations between 4 and 10 microg/l. To evaluate the diagnostic utility of free PSA (fPSA) and complexed PSA forms for identification of men with PCa in the low PSA range of <4 microg/l, total PSA (tPSA), alpha(1)-antichymotrypsin complexed PSA (PSA-ACT) and fPSA (Roche Elecsys [ES] system) as well as tPSA and complexed PSA (cPSA) (Bayer Immuno 1 system) were measured in archival serum samples from 31 untreated patients with PCa, 66 patients with BPH, and 90 men without prostatic disease. The median ratios of fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were significantly different between patients with BPH and PCa (27.2 vs. 19.4%, 64 vs. 88%, 77.2 vs. 88.2%, p < 0.05). No associations between PSA forms and tumor stage and grade were found. Analysis of the receiver operating characteristic curves showed that these ratios could discriminate better between BPH and PCa patients than determination of the analytes tPSA, fPSA, cPSA and PSA-ACT alone. The use of one of the ratios would have eliminated roughly half of the unnecessary biopsies in this study. The ratios should be considered as potential tools to increase the selectivity of PCa detection at low PSA concentration. The ratios fPSA/tPSA and cPSA/tPSA can be determined using commercially available assays so that one of these ratios could be preferred instead of PSA-ACT determination. The ratios could be useful in assessing the risk of PCa in the individual and therefore in deciding on prostate biopsy for final diagnosis.     

Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level,Gleason score,or TNM status

Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients’ blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.     

Factors influencing the ratio of free to total prostate-specific antigen in serum

The ratio of free prostate-specific antigen (f-PSA) to total PSA (t-PSA) in serum, calculated as percent free PSA (f-PSA%), is lower in patients with prostate carcinoma (PCa) than in patients with benign prostate hyperplasia (BPH). This parameter facilitates discrimination between the 2 groups of patients, but there is an overlapping of data. A better understanding of factors influencing this ratio is of practical importance. Therefore, f-PSA% was measured in controls and patients suffering from BPH, PCa and chronic prostatic inflammation with t-PSA concentrations up to 20 μg/l using the IMMULITE assays. The relationships of f-PSA% to clinical situation, age, prostate volume, kind of treatment, and stage and grade of tumor were calculated. Compared with controls or BPH patients, mean f-PSA% values were reduced in PCa patients and in patients with chronic prostatic inflammation. The prostate volume was the most important factor to influence f-PSA%. The difference of f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm³ was lost if the prostate volumes exceeded 40 cm³. No relationship of f-PSA% to pTNM stage or grade of tumor was observed. In contrast to t-PSA concentrations, the f-PSA% values were not age-dependent and were not influenced by any kind of treatment in BPH and PCa patients either, which simplifies the use of f-PSA% compared with t-PSA. Thus, for using f-PSA% in clinical practice and for interpreting the data correctly, the advantages shown have to be considered along with the potential limitations of f-PSA%. Int. J. Cancer 74:630–636.© 1997 Wiley-Liss, Inc.     

Identification of Differential Patterns of Oxidative Biomarkers in Prostate Cancer Progression

IntroductionOxidative stress has been found to be associated with the progression of prostate cancer (PCa); however, human studies which identify differential roles of each oxidation pathway in PCa progression are lacking. We aimed to identify which oxidative stress markers, specifically lipid and global oxidation and glycation, are associated with PCa progression.Patients and MethodsWe recruited 3 groups of patients from a urologic clinic at the University of Cincinnati Medical Center: men with PCa who had undergone prostatectomy, men with PCa under watchful waiting, and men with benign prostatic hyperplasia (BPH). We used the most commonly used lipid oxidation marker, F2-isoprostanes; global oxidation markers, fluorescent oxidation products (FlOPs); and the commonly used marker for advanced glycation end products, carboxymethyllysine. These biomarkers were measured in plasma samples at baseline entry. Plasma prostate-specific antigen (PSA) was measured at enrollment and follow-up visits.ResultsCompared with men with BPH, men with PCa who had undergone prostatectomy had 26% (P = .01) higher levels of F2-isoprostanes and 20% (P = .08) higher levels of carboxymethyllysine. All the oxidation markers were similar when comparing men under watchful waiting with men with BPH. When examining the associations between baseline oxidation markers and follow-up PSAs, we found that different oxidation markers had differential patterns associated with PSA elevation. F2-isoprostanes were positively associated with PSA elevation among men with PCa; FlOP_320 was positively associated with PSA elevation among both men with PCa and men with BPH, whereas among men with PCa under watchful waiting, FlOP_360 and FlOP_400 had opposite trends of associations with PSA elevation.ConclusionsOur study suggested that high levels of lipid oxidation were associated with PCa progression, whereas different global oxidation markers had different patterns associated with PCa progression. Large-scale clinical studies are needed to confirm our associations. Our study provides a comprehensive view of the relationship between biomarkers and PCa progression.