Comparative Expression of RAGE and SOX2 in Benign and Malignant Prostatic Lesions

Background: Prostate cancer (PCa) is a common health problem in elderly. RAGE (Receptor for advanced glycationend products) is overexpressed in multiple human cancers. SOX2 (Sex-determining region Y box 2) also functions as anoncoprotein and promotes cancer progression but the mechanisms involved remain largely unknown. Aim: The currentstudy investigated the expression patterns of RAGE and SOX2 in benign and malignant prostate samples in correlationwith the histopathological findings in order to evaluate their role as prognostic markers or therapeutic targets. Methods:Immunohistochemical staining for RAGE and SOX2 antibodies was applied on 87 prostatic biopsies [16 of prostatitis, 20of benign prostatic hyperplasia (BPH) and 51 of PCa]. Results: Expression of RAGE and SOX2 (percentage of positivecells) was significantly higher in PCa lesions compared with prostatitis (p<0.01) and BPH (p<0.0001) and was alsosignificantly higher in prostatitis compared with BPH lesions (p<0.01). Also, percentage of positive RAGE and SOX2cells showed a significant stepwise increase from Gleason Grade 3 to Grade 5 and were significantly higher in highGleason Scores (≥8) compared to lower Scores (≤7) with statistical significance (p=0.001). Conclusion: RAGE andSOX2 were up-regulated in prostate cancer lesions, mainly in advanced grades, suggesting an active role of both antigensin the development and progression of prostate cancer and expecting the possibility of their use as therapeutic targets.     

Progression of prostate cancer: diagnostic and prognostic utility of prostate-specific antigen, alpha2-macroglobulin, and their complexes

We previously reported cases of advanced prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than approximately 50 mg/dl whereas serum prostate-specific antigen (PSA) levels were remarkably increased. These cases were not complicated with disseminated intravascular coagulation (DIC). In this study, we measured serum PSA and alpha2M in 108 patients with either benign prostatic hyperplasia (BPH) or PCa to elucidate the relationship between PSA, i.e. the serum protease derived from the prostatic tissue, and alpha2M, i.e. the protease inhibitor that was the most abundantly contained in serum. alpha2M was determined by ELISA, total PSA and PSA-alpha1-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with untreated BPH and 64 patients with untreated PCa. The ready association of alpha2M and PSA was assessed using Western blotting to identify complexes of the two. Levels of total serum PSA correlated positively with those of PSA-ACT in PCa (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease. In contrast, the serum-free PSA/total PSA ratio (free/total PSA) and alpha2M levels decreased as the disease progressed. However, only the free/total PSA ratio attained significant difference for localized cancer in stage T1,2 versus BPH (p < 0.05). In stage M1b PCa, in which serum PSA levels were very high, there was a negative correlation between the total PSA and alpha2M values (r = -0.57, p < 0.05). In addition, serum alpha2M levels tended to decrease with progression of PCa. Serum total PSA levels correlated tightly with serum PSA-ACT levels. It is suggested that PSA is usually complexed with ACT in the serum. Free/total PSA was useful for differential diagnosis between early cancer and BPH. Levels of serum alpha2M of less than 50 mg/dl in PCa patients may indicate a possibility of bone metastases.     

海南地区Gleason评分≥7分的前列腺癌患者血清PSA和睾酮水平与预后相关性探讨

目的:分析海南地区Gleason评分≥7分的前列腺癌（prostatic cancer,PCa）患者血清前列腺特异性抗原(prostate specific antigen,PSA)和总睾酮（total testosterone,TT）水平与5年总生存率的相关性。方法:回顾性分析2009年01月至2019年12月我院收治的前列腺癌患者106例作为PCa组,选取同期良性前列腺增生症（benign prostatic hyperplasia,BPH）患者120例作为BPH组,比较两组患者临床资料、血清PSA、TT水平;再根据PCa组患者5年生存情况分为生存组（n=81）和死亡组（n=25）,比较两组患者临床资料、Gleason评分、血清PSA、TT水平;采用多因素COX回归分析影响前列腺癌患者预后的独立危险因素;绘制受试者工作特征曲线（receiver operating characteristic curve,ROC）,分析血清PSA、TT水平早期评估前列腺癌患者预后的预测价值;采用Spearman相关性模型分析血清PSA、TT水平与病理Gleason评分的相关性。结果:PCa组患者年龄、前列腺体积、血清PSA水平高于BPH组,血清TT水平低于BPH组,差异具有统计学意义（P＜0.05）;生存组患者Gleason评分、血清PSA水平、骨转移发生率、TNM分期低于死亡组,血清TT水平高于死亡组,差异具有统计学意义（P＜0.05）;Spearman相关性分析显示,血清PSA水平与病理Gleason评分呈正相关（r=0.634,P＜0.05）,血清TT水平与病理Gleason评分呈负相关（r=-0.755,P＜0.05）;多因素COX回归分析显示,高PSA水平（HR=1.352）、高Gleason评分（HR=4.576）、高TNM分期(HR=2.937)和骨转移（HR=1.258）是前列腺癌患者预后的独立危险因素（P＜0.05）,高TT水平（HR=0.063）是前列腺癌患者预后的保护因素（P＜0.05）;ROC曲线显示,血清PSA、TT水平及两者联合早期预测前列腺癌患者预后的曲线下面积（area under curve,AUC）为0.811、0.887和0.934,敏感度为88.00%、96.00%和92.00%,特异度为68.73%、72.84%和82.72%,截点值分别为21.51 ng/mL和3.74 ng/mL。结论:前列腺癌患者血清PSA、TT水平可作为早期评估患者预后的重要指标,其与病理Gleason评分存在高度相关性。     

Is the Neutrophil-Lymphocyte Ratio an Indicator of Progression in Patients with Benign Prostatic Hyperplasia?

Purpose: The aim of this study was to evaluate inflammation parameters and assess the utility of the neutrophillymphocyte ratio (NLR) as a simple and readily available predictor for clinical disease activity in patients with nenign prostate hyperplasia BPH. We also aimed to investigate the relationship between inflammatory parameters with α-blocker therapy response, and evaluate the potential association between NLR and the progression of benign prostatic hyperplasia (BPH). Materials and Methods: We examined 320 consecutive patients (July 2013-December 2013) admitted to our outpatient clinic with symptoms of the lower urinary tract at Bozok University. The mean age was 60 (range, 51-75) years. Complete blood count (CBC), prostate-specific antigen (PSA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. Correlations between PSA, CRP, ESR, prostate volume, International Prostate Symptom Score (IPPS), maximum urinary flow rate (Qmax), and NLR were assessed statistically. Patients were divided into two groups: high and low risk of progression. Results: NLR was positively correlated with IPSS (p=0.001, r=0.265), PSA (p=0.001, r=0.194), and negatively correlated with Qmax (p<0.001, r=-0.236). High-risk patients a had a higher NLR compared with low-risk patients, based on IPSS (p<0.001), PSA (p=0.013), and Qmax (p<0.001); however, there were no significant differences between the groups in terms of age (p>0.05), and prostate volume (p>0.05). Conclusions: NLR can predict BPH progression. We propose that increased inflammation is negatively associated with clinicalstatus in BPH patients and suggest that NLR can give information along with LUTS severity which may be used as a readikly accessible marker for patient follow-up.     

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.     

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。     

游离前列腺特异性抗原与总前列腺特异性抗原比值在前列腺癌鉴别诊断中的应用

 目的 探讨游离前列腺特异性抗原（fPSA）与总前列腺特异性抗原（tPSA）比值在前列腺癌（PCa）鉴别诊断中的意义。方法 采用电化学免疫发光技术对86例前列腺良性增生（BPH）45例PCa患者和60例健康男性体检者（正常对照组）血清fPSA和tPSA同时进行测定，并计算出fPSA／tPSA，进行统计分析。结果 BPH、PCa组tPSA水平明显高于正常对照组（P＜0.05）。PCa组和BPH组的血清tPSA差异亦有统计学意义，但当tPSA在4.0 ~ 10.0 μg／L范围时，PCa组血清fPSA／tPSA比值却明显低于BPH组（P＜0.01）。把fPSA／tPSA比值划分成8个区间，当fPSA／tPSA比值15 ％作为诊断灰区PCa诊断的临界值时，诊断的敏感性、特异性、阳性预测值、阴性预测值及正确诊断指数分别为72.8 %、67.5 %、62.5 %、82.2 %、50.2 %。结论 当血清tPSA处于诊断灰区时，联合检测fPSA／tPSA比值可明显提高tPSA对PCa早期诊断的特异性。     

Effects of chronic bacterial prostatitis on changes in concentration and free and total prostatic specific antigen in the serum and urine from patients with benign prostatic hyperplasia and prostatic cancer

A comprehensive urological examination was performed in 145 men with benign prostatic hyperplasia (BPH). Concentrations of total prostatic specific antigen (TPSA) suggested prostatic cancer (PC) in 38 patients while finger rectal examination and transrectal ultrasonic investigation gave no evidence for this diagnosis. All the patients have symptoms of chronic prostatitis (CP). All the patients with chronic bacterial prostatitis have undergone a course of antibacterial treatment after which the levels of TPSA and free prostatic specific antigen (FPSA) were evaluated. A polyposition biopsy of the prostate was also made. By its results two groups of patients were formed: 20 patients with BPH and CP (group 1) and 12 patients with CP and PC or prostatic ultraepithelial neoplasia. Low blood concentrations of TPSA high FPSA/TPSA, low urinary concentrations of TPSA and FPSA were registered after antibacterial and antiinflammatory treatment of CP combined with BPH. It is inferred that chronic bacterial prostatitis has a significant effect on PSA expression in BPH. This fact should be considered in interpretation of PSA values.     

前列腺特异性抗原的检测对前列腺癌及前列腺增生的诊断意义

目的　探讨血清总前列腺特异性抗原 (t PSA)、游离PSA (f PSA)、PSA密度 (PSAD )及其f PSA/t PSA比值对前列腺癌 (PCa)及前列腺增生 (BPH )的诊断价值。方法　采用酶联免疫分析方法 (ELISA )检测未经治疗的 62例BPH患者和 2 4例PCa患者血清f PSA、t PSA水平 ,并计算f PSA/t PSA值和PSAD ,对检测结果进行统计学处理。结果　BPH组与PCa组的f PSA、t PSA水平均明显高于对照组 (P <0 .0 1) ;前列腺癌组的f PSA /t PSA值明显小于对照组及前列腺癌增生组 (P <0 .0 1) ;PCa组PSAD明显大于对照组和BPH组 (P <0 .0 1)。结论　检测f PSA/t PSA和PSAD比单一检测f PSA、t PSA可显著提高对PCa诊断的特异性及符合率 ,对前列腺体积较大的BPH和PCa患者 ,检测PSAD更有意义     

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.     

Evaluation of free-to-total prostate specific antigen ratio in the diagnosis of prostate cancer

It'sreportedthatfreetototalprostatespecificantigenration(f/tPSA)canprovidemorebenefitthanthesingleuseofprostatespecificantigen(PSA)inthediagnosisofprostatecancer(PCa).WemeasuredserumPSAandfPSAlevelsin62casesofbenignprostatichyperplasia(BPH)and40casesofPCausingradioimmunoassay,withpatients'agerange59y-89y.RESULTSPSA,fPSAandf/tPSAareshowninTable1.BoththesetwogroupsshowslinearcorrelationbetweenPSAandfPSA,correlationcoefficientofBPHis0.55(P<0.01),ofPCais0.44(P<0.01).Twoslopesha…     

Can the Irisin be a Biomarker for Prostate Cancer? A Case Control Study

Aim: There is much evidence of an association between cancer and irisin that is an adipokine. This study researched on the relationship between prostate cancer (PCa) and irisin levels, and whether irisin can be used as a biomarker in the diagnosis of PCa. Materials and Methods: For the study groups, 50 primary PCa patients and 30 healthy male subjects were included in the PCa and healthy control groups, respectively. All volunteers in the healthy control group were screened for prostate cancer and other malignancies and chronic diseases. Volunteers who were determine to be completely healthy were included for healthy control group. In the serum samples of the subjects were measured free PSA, total PSA and irisin levels. Irisin levels were compared separately in terms of the Gleason scores and T stage. In addition to intergroup comparisons, the ROC curve for the irisin was plotted and power analysis was performed. Results: Free and total PSA levels in the PCa group were significantly higher compared to the healthy control group (p<0.05). In addition, irisin levels in the PCa group were significantly lower  than in the healthy control group (p<0.05). There was no significant difference between irisin levels in the groups classified in terms of Gleason scores (p>0.05).  When the cut-off value was taken as 8.1, the sensitivity and specificity of irisin for PCa were as 80.5% and 90%, respectively. Conclusion: The results of this study indicate that the levels of irisin in the PCa group are considerably reduced and irisin may be used as a biomarker as well as free and total PSA.     

前列腺癌组织中p27和Survivin的表达与前列腺特异性抗原的相关性

目的:通过分析蛋白p27和Survivin在前列腺癌(PCa)组织中的阳性表达与前列腺特异性抗原(PSA)的相关性,探讨前列腺癌的治疗方法.方法:应用免疫组织化学方法检测75例前列腺癌和60例前列腺增生组织中p27、Survivin蛋白的表达和相应患者血浆中的PSA值.结果:前列腺癌组织中p27、Survivin蛋白的阳性表达率分别为37.3%(28/75)、68.0%(51/75),p27和Survivin蛋白在前列腺增生组织中的阳性表达率分别为63.3%(38/60)、0(0/60),在前列腺增生和前列腺癌组织中Survivin和p27蛋白的阳性表达率差异均具有统计学意义(P<0.05).p27和Survivin蛋白表达与前列腺癌病理分级、临床分期、转移情况和PSA值具有统计学意义(P<0.05).结论:临床中联合检测p27及Survivin表达与前列腺特异性抗原的关系和相互作用机制,为前列腺癌的防治和治疗提供新的思路.     

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.     

Expression of neutral amino acid transporter ASCT2 in human prostate

The neutral amino acid transporter ASCT2 has been associated with increased metabolism in malignant tumors. Its biological significance in tumor proliferation, progression, and its impact on cancer patients' survival remains largely unknown. Tissue microarray (TMA) technology was used to build arrays from 640 cases of radical prostatectomies (triplicate normal prostate, benign prostatic hyperplasia (BPH), and prostate adenocarcinoma (PCa)). Slides were immunostained with an antibody to ASCT2 and scored using a 0-3+ semi-quantitation scoring system for both intensity and percentage. Correlation of ASCT2 expression with patients' clinical and pathological variables was analyzed by the Spearman correlation test. Kaplan-Meier analysis and log rank test were used to determine the probability of disease recurrence. Cox regression model was also used for multivariate analysis. 497 PCa had accessible data. ASCT2 was localized in the cytoplasm of epithelial cells of normal prostate, BPH and PCa. High-level expression of ASCT2 was significantly higher in normal tissues (49%) as compared to BPH (25.8%) or cancer (25.3%) (p < 0.001). ASCT2 expression was weakly but significantly correlated with preoperative PSA (Pre-PSA), Gleason score (GS), lymph node status (LN) (p = 0.019). ASCT2 expression was significantly associated with shorter time to biochemical recurrence only on univariate analysis (p = 0.046). ASCT2 appears to be required for the glutamine metabolism in both nonmalignant and malignant prostate. ASCT2-positive PCa seems to be related to a more aggressive biological behavior. ASCT 2 seems to be involved in tumor progression.     

The clinical utility of measuring total PSA, PSA density, gamma-seminoprotein and gamma-seminoprotein/total PSA in prostate cancer prediction

BACKGROUND: To evaluate whether serum total prostate-specific antigen (PSA), PSA density (serum total PSA level divided by prostate volume), gamma-seminoprotein and gamma-seminoprotein/total PSA ratio could predict prostate cancer (PCa) prior to biopsy. METHODS: A total of 316 consecutive patients who had undergone transrectal prostate biopsy and/or transurethral resection were examined. The prostate volume was determined by transrectal ultrasonography (TRUS) and the ability of the above-mentioned four variables to distinguish PCa from benign prostatic hyperplasia (BPH) was evaluated. RESULTS: PCa was detected in 61 cases. Receiver-operating characteristic (ROC) analysis revealed that both the PSA density and serum total PSA were the most useful predictors of PCa among the four variables. For the patients with a serum total PSA level of 4.1-10.0 ng/ml, PSA density was significantly more accurate than total PSA (p < 0.005). An optimum PSA density value of 0.18 was chosen as a cutoff because it showed the highest sum of sensitivity and specificity, 92 and 54%, respectively. Using this PSA density cutoff, the number of biopsies could have been reduced to 57 from 63% when compared with a PSA density of 0.15. CONCLUSIONS: PSA density was significantly more accurate than other variables in predicting PCa. To avoid unnecessary biopsies, the PSA density cutoff value of 0.18 would be recommendable for determining a prostate biopsy for Japanese males with a serum total PSA level of 4.1-10.0 ng/ml.     

中国汉族人群前列腺癌易感性与TLR4基因单核苷酸多态性的研究

目的 探讨Asp299Gly(rs4986790)、Thr399Ile(rs4986791)、rs11536889单核苷酸多态性(SNP)与前列腺癌(PCa)易感性和严重程度的关系.方法 采用病例对照研究方法,选取组织学证据确诊的PCa患者96例为PCa组,良性前列腺增生(BPH)患者87例为BPH组,健康者92例为健康对照组.记录研究对象的临床资料并计算Gleason评分,PCR-RFLP法分析各组的基因型.结果 PCa组、BPH组及健康对照组的年龄、前列腺癌家族史所占比例、前列腺特异抗原(PSA)水平比较,差异均有统计学意义(P=0.000);PCa组、BPH组及健康对照组的Asp299Gly和Thr399Ile基因型频率分布比较,差异无统计学意义(P﹥0.05),但3组间rs11536889基因型频率分布比较,差异有统计学意义[PCa组/(BPH组+健康对照组),CC/GC vs GG,OR=2.152,95%CI:1.280~3.618,P﹤0.05];Gleason评分≥7分组GC+CC分布比例高于Gleason评分﹤7分组(OR=2.378,95%CI:1.042~4.427,P﹤0.05).结论 TLR4基因rs11536889 SNP可能与PCa发病和病情严重程度相关.     

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.     

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.