Complexed and total PSA in patients with benign prostatic hyperplasia and prostate cancer

This study compares the diagnostic utility of complexed prostate-specific antigen (cPSA), total PSA (tPSA) and their ratios with free PSA (fPSA) for benign prostatic hyperplasia (BPH) and prostate cancer. This is though to be the first study to evaluate cPSA in the ethnic population of Saudi Arabia. Serum samples were collected from 54 patients (aged over 50) and assayed for tPSA, cPSA and fPSA. Thirty-five patients were histologically and clinically proven to have BPH and 19 patients were proven to have cancer. Sensitivity, specificity and ROC curves were calculated. With a cPSA cut-off of 4 ng/mL the sensitivity was 79%, the specificity was 34%, and the positive and negative predictive values (PPV and NPV) were 39% and 75%, respectively. At the same cut-off for tPSA, the sensitivity was 84%, the specificity was 29%, and the PPV and NPV were 39 and 77%, respectively. The sensitivity for both tests was lower at a cut-off of 20 ng/mL but the specificity increased to 77% for cPSA and 69% for tPSA. The areas under the receiver operating characteristic (ROC) curves were found to be 0.608 for tPSA and 0.559 for cPSA (P = 0.69). The incidence of prostate cancer in the Saudi population may be lower than that in Western populations. The data presented show little advantage in using cPSA over tPSA for discriminating BPH and prostate cancer in the population studied.     

前列腺癌患者血清T-PSA、F-PSA水平和F/T比值变化及临床意义

目的:观察前列腺癌患者(PCa)血清总前列腺特异抗原(T-PSA)、游离前列腺特异抗原(F-PSA)和F-PSA/T-PSA比值(F/T值)变化,探讨其临床意义。方法: 用MEIA法检测121例PCa患者和554例良性前列腺增生(BPH)患者术前及其中82例PCa患者和396例BPH患者术后血清T-PSA、F-PSA水平,并计算F/T值。结果: 术前PCa患者T-PSA与F-PSA明显高于BPH患者,F/T比值明显低于BPH患者,两组间差异均显著(P＜0.01)。术后两组患者T-PSA、F-PSA水平较术前明显降低,F/T值则明显升高,与术前结果比较,差异均显著(P＜0.01)。在T-PSA＜10.0 μg/L范围,PCa患者占33.9%,BPH患者占85.5%,两组患者结果存在交叉。F/T值＜0.16时,PCa患者占83.5%,BPH患者占6.5%,两组差异显著(P＜0.01),F/T值＜0.16时诊断的灵敏度、特异性、阳性预示值、阴性预示值分别为83.5%、86.7%、81.1%、88.2%。结论: PCa和BPH患者手术前后血清T-PSA、F-PSA水平及F/T值均有明显变化。以F/T比值＜0.16作为PCa诊断临界值,可有效提高早期PCa诊断的特异性和敏感性,减少不必要的活检。     

成纤维细胞生长因子10在前列腺增生组织中的表达

目的 检测前列腺增生组织中成纤维细胞生长因子10（FGF－10）的表达，探讨其在前列腺增生中的作用。方法 应用半定量R－TPCR技术和免疫组织化学方法，检测20例前列腺增生组织中FGF－10的表达，并与正常的前列腺组织进行比较。结果 前列腺增生组织中FGF－10 mRNA的水平高于正常前列腺组织，前列腺增生组织中FGF－10 mRNA的水平高于正常前列腺组织；前列腺组织中均见FGF－10阳性染色，前列腺增生组织中表达显著高于正常的前列腺组织。结论 前列腺增生组织中FGF－10的表达高于正常前列腺组织，提示FGF－10对促进前列腺的增生起重要作用。     

Fibronectin pattern in benign hyperplasia and cancer of the prostate

Fibronectin (FN) is a multifunctional glycoprotein involved in cell-matrix interactions. It exhibits a complex pattern of forms differing in respect to aminoacid and oligosaccharide composition. In this study we examined glycobiochemical and functional properties of the FN in benign prostatic hyperplasia (BPH) and prostatic cancer (PCa), attempting to resolve disease-related differences. Two BPH sera pools and three PCa sera pools were used as the FN source. The affinity-purified molecule was characterized by SDS-PAGE, immuno- and lectin blot, lectin-affinity chromatography and adhesion assay. BPH FN existed as intact molecule, giving the main immunoreactive band at 220 kDa. In contrast, PCa FN comprised three main immunoreactive fragments of 140, 110 and 90 kDa. As for glycosylation the ratio of altogether lectin-reactive PCa FN was different from that of BPH FN manifested as a decrease of Con A- and an increase of LCA-reactive moieties. Fibroblasts adhered to both FN preparations in a concentration dependent manner, but with a significantly lower efficiency to PCa FN. The results obtained showing distinct structural characteristics of PCa FN compared to BPH FN could be important for modulation of its ligand and recognition properties expressed as gain or loss of functions or as specific markers of its origin.     

Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.

The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.     

Urinary microbiota in patients with prostate cancer and benign prostatic hyperplasia

Introduction

Inflammation is associated with promotion of the initiation of various malignancies, partly due to bacterial infection-induced microenvironmental changes. However, the exact association between microbiota in urine, seminal fluid and the expressed prostatic secretions and benign prostatic hypertrophy and prostate cancer is not clear.

Material and methods

In the present study, we investigated the type of microbiota in the expressed prostatic secretions (EPS) of patients with prostate cancer and benign prostatic hyperplasia (BPH) by the polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) method using universal bacterial primers. In order to understand the possible association between various bacteria and prostate cancer, quantitative real-time PCR assay was performed to quantify the amount of strains of bacteria in urine, EPS and seminal fluid.

Results

The prostate cancer group had a significantly increased number of Bacteroidetes bacteria, Alphaproteobacteria, Firmicutes bacteria, Lachnospiraceae, Propionicimonas, Sphingomonas, and Ochrobactrum, and a decrease in Eubacterium and Defluviicoccus compared to the BPH group. The number of Escherichia coli in the prostate cancer group was significantly decreased in urine and increased in the EPS and seminal fluid, while the number of Enterococcus was significantly increased in the seminal fluid with little change in urine and EPS.

Conclusions

Based on these results, we suggest that there are significant changes in the microbial population in EPS, urine and seminal fluid of subjects with prostate cancer and BPH, indicating a possible role for these bacteria in these two conditions.     

Mesonephric remnant hyperplasia: an unusual benign mimicker of prostate cancer

Mesonephric remnant (MR) hyperplasia in the prostate is a rarely reported condition that is usually distinguished from prostatic adenocarcinoma by the absence of cytologic atypia as well as the absence of prostatic markers (prostate-specific antigen and prostatic acid phosphatase) expression. We report a case of prostatic MR hyperplasia with architectural and cytologic atypia in a 56-year-old man. The microscopic appearance strongly suggested malignancy, but immunohistochemistry allowed the diagnosis to be corrected. The presence of MRs in prostate tissues may be more common than appreciated or reported. Once the possibility is considered, the diagnosis is easily confirmed using immunochemistry.     

Potential biomarkers for differentiation of benign prostatic hyperplasia and prostate cancer

This study aims to evaluate the role of free/total prostate-specific antigen (PSA) ratio, serum total sialic acid level and cathepsin D activity in the differentiation of prostate cancer and benign prostatic hyperplasia (BPH). The study looked at 100 patients with BPH, 75 patients with organ-confined or locally advanced prostate cancer, and a control group of 50 healthy volunteers. Prostate cancer patients showed significantly higher total sialic acid level and cathepsin D activity and lower free/total PSA ratio than those in the BPH group. The results suggest that combined measurement of serum total sialic acid and/or cathepsin D activity with free/total PSA ratio could serve as a useful adjunct to conventional diagnostics for the differentiation of prostate cancer and BPH.     

3.0T多b值弥散加权成像在前列腺癌与前列腺增生鉴别诊断中的应用

目的评价3.0T MRI多b值弥散加权成像（DWI）在前列腺癌（PCa）与前列腺增生（BPH）鉴别诊断中的应用价值。方法该研究获得伦理委员会核准。选择经临床病理学证实12例PCa（20个病灶）和9例BPH（15个病灶）男性患者,其中PCa患者年龄56～83岁,平均年龄71.08岁;BPH患者年龄65～83岁,平均年龄71.78岁。回顾分析21例患者3.0 T MRI多b值DWI表现。多b值DWI扫描使用盆腔8通道相控阵线圈,采用EPI-STIR序列,并行采集技术,b值分别为0、300、600、900、1 200、1 500、1 800、2 100 s/mm2,扫描时间260 s。利用GE Functool 4.4工作站测量多b值DWI上PCa和BPH不同b值时的信号强度,描绘其b值-信号强度曲线并计算曲线斜率和信号衰减率（Sde）,测量标准表观弥散系数（ADC）值,对比PCa和BPH的b值-信号强度曲线斜率、Sde和标准ADC值。结果 b值为0、300、600、900、1 200、1 500、1 800、2 100 s/mm2时,PCa的信号强度分别为（520.41±156.11）、（345.43±89.29）、（262.06±74.85）、（212.63±78.87）、（182.14±75.56）、（156.98±73.24）、（137.31±68.26）、（120.11±63.08）MR unit;BPH的信号强度分别为（605.71±146.32）、（357.83±84.91）、（221.44±65.62）、（177.04±55.58）、（145.02±53.43）、（116.39±59.26）、（98.03±56.42）、（86.11±53.62）MRunit,各个b值时PCa和BPH的信号强度差异无统计学意义（P〉0.05）;PCa的b值-信号曲线斜率为50.01±18.86,BPH为64.95±21.25,PCa者低于BPH者,二者之间的差异无统计学意义（P〉0.05）;PCa和BPH的Sde分别为76.43%±11.38%和88.54%±3.68%;标准ADC值分别为（×10-3mm2/s）0.588±0.135和1.11±0.15,PCa的Sde和标准ADC值明显低于BPH者,二者之间的差异有统计学意义（P〈0.05）。结论 3.0 T MRI多b值DWI中b值-信号曲线Sde及标准ADC值对无创鉴别PCa和BPH有帮助。     

Association of GSTM1 and GSTT1 polymorphism with lipid peroxidation in benign prostate hyperplasia and prostate cancer: a pilot study

Association of glutathione S-transferase (GST) M1 and T1 deletions with benign prostate hyperplasia (BPH) and prostate cancer is well reported. These enzymes metabolize numerous toxins thus protecting from oxidative injury. Oxidative stress has been associated with development of BPH and prostate cancer. The present study was designed to analyze role of GST deletions in development of oxidative stress in these subjects. GSTs are responsible for metabolism of toxins present in tobacco therefore effect of tobacco usage in study groups was also studied. Three groups of subjects: BPH (57 patients), prostate cancer (53 patients) and controls (46 subjects) were recruited. Genotyping was done using a multiplex polymerase chain reaction (PCR) method. Malondialdehyde (MDA) levels as marker of oxidative stress were estimated by measuring thiobarbituric acid reactive substance (TBARS) in plasma. Based on genotyping, subjects were categorized into: GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1- and GSTM1-/GSTT1-. Significantly higher plasma MDA levels were noticed in GSTM1-/GSTT1- as compared to GSTM1+/GSTT1+ in all study groups. Double deletion (GSTM1-/GSTT1-) is associated with higher oxidative stress which might play a role in the pathogenesis of BPH and prostate cancer. However, other markers of oxidative stress should be analyzed before any firm conclusion.     

Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer

Spermatogenesis‐associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non‐malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non‐malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non‐malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty‐nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H‐score) was not associated with overall survival or disease‐specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease.     

Vascular endothelial growth factor in patients with prostate cancer and benign prostatic hyperplasia

The authors examined 25 patients with prostate cancer (PC) and 36 patients with benign prostatic hyperplasia (BPH). In the group of patients with morphologically verified PC mean serum level of vascular endothelial growth factor (VEGF) was significantly higher than in patients with BPH (p < 0.05). The study demonstrated strong negative association between VEGF and prostate specific antigen (PSA) levels (r = 0.72, p < 0.05) in PC patients. There was no association between VEGF serum level and the stage or malignancy of PC (Gleason score). In benign prostatic glands moderate VEGF expression was observed only in basal cells, whereas in cases of PC all tumor cells displayed active VEGF expression; the difference was significant (p < 0.05). High serum VEGF levels and its active expression in patients with PC suggest an important role of angiogenic factors in the pathogenesis of this disease. The negative association between VEGF and PSA serum levels in PC indirectly confirms antiangiogenic activity of PSA, shown before.     

前列腺癌与前列腺增生HER-2及C-myc基因mRNA表达的研究

目的 检测良性前列腺增生(BPH)与前列腺癌(PCa)组织标本HER-2及C-mvc mRNA相对值,探讨此值对PCa诊断的特异性意义.方法 通过实时荧光定量PCR检测63例PCa、37例BPH及3例正常前列腺组织HER-2及C-myc mRNA的表达,比较其在PCa与BPH中组织定量的差异.结果 相对于BPH,PCa HER-2及C-myc mRNA表达相对值分别为4.25±0.03,7.24±0.06,PCa HER-2及C-myc表达相对值较BPH高,差异有统计学意义(均为P<0.05).结论 实时荧光PCR定量检测HER-2及C-myc mRNA为PCa的诊断提供了重要的辅助指标.     

The biological significance of atypical hyperplasia of the prostate

Summary In tissue biopsies and resection material (TUR) of the prostate a high coincidence (49.4%) was found between atypical primary hyperplasia with atypical-dysplastic microglandular, adenomatous and cribriform structures on the one hand and carcinomas on the other. The frequency of atypical hyperplasia in prostatic tissue without carcinoma was 2.8%. Microglandular pattern predominates in atypical hyperplasia combined with differentiated adenocarcinomas. A high coincidence between cribriformly structured glands of atypical primary hyperplasia and solid anaplastic — cribriform carcinomas can be observed.Autoradiographically the labeling index of atypical hyperplasia was three times as high as that of simple hyperplasia. The mean labeling index of atypical hyperplasia, however, was similar to that of poorly differentiated adenocarcinomas and cribriform carcinomas. The similar proliferation pattern of atypical hyperplasia and carcinomas as well as the high coincidence between both indicate that severe atypical primary hyperplasia is a precancerous lesion.Therefore, those patients with primary atypical hyperplasia with distinct cellular and structural atypia but without manifest carcinomas in prostatic biopsy or resection material should be followed up at short intervals.Supported by Landesamt für Forschung, Minister für Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Düsseldorf     

Utility of free/total prostate specific antigen (f/t PSA) ratio in diagnosis of prostate carcinoma

The discovery that PSA exists in serum in both free and complexed forms led to development of immunoassays specific for different PSA forms. This helped in measuring free PSA in the presence of PSA-ACT (PSA-alpha antichymotrypsin), hence it was possible to calculate the percent free PSA or free to total PSA ratio, measurement of which was helpful in reducing the number of unnecessary biopsies significantly, while maintaining a high clinical sensitivity for detection of cancer. The study was performed on 103 consecutive male patients (mean age 68 +/- 10.8 years SD) comprising of 90 patients with benign disease (87%) and 13 prostate carcinoma patients (13%), who had histologically proven prostate cancer. Patients with total PSA between 2-25 ng/ml were included in the study. 30 normal healthy males with age 58 +/- 10 years, served as control. Serum total PSA and free PSA were analyzed using streptavidin biotin EIA method (M/s Roche Diagnostics, Germany). The mean total PSA in normal healthy control subjects was 1.86 +/- 1.07 ng/ml. It was increased significantly in diseased condition. Its mean concentration in carcinoma patients was 12.6 +/- 5.3 ng/ml and in benign patients it was 6.3 +/- 4.6 ng/ml. The free to total PSA ratio in all the three groups was significantly different (p < 0.004) from each other. In carcinoma patients, mean f/t PSA ratio was 0.12 +/- 0.06 as compared to 0.21 +/- 0.11 and 0.28 +/- 0.17 in benign patients and in control respectively. The sensitivity and specificity of the test was calculated at different f/t PSA ratio cutoff. At 0.1 cutoff value, sensitivity of the test was 54% and specificity was 83%. The positive predictive value (ppv) was 32% and negative predictive value (npv) was 92%. From cutoff value of 0.12 to 0.16, sensitivity was increased from 54% to 85% but specificity was reduced from 78% to 67%. The ppv did not show much change and npv was increased from 92% to 97%. Increasing the cut off value thereafter showed no change in sensitivity but specificity was further reduced to 40%, therefore in this patient series, f/t PSA ratio cutoff of 0.16 was found to be the appropriate cutoff value. Combination of this ratio cutoff with other parameters like serum total PSA, DRE and TRUS helped in increasing the sensitivity of the test and this also helped in reducing the number of unnecessary biopsies. In 103 men who were biopsied, 13 (12.6%) prostatic carcinoma were identified. Among these 13 cancer patients, 9 patients had abnormal findings in DRE.7 individuals out of these 9, also had free to total PSA ratio lower than 0.16 and would have been biopsied and diagnosed anyway. If we use only f/t PSA ratio less than 0.16, to decide whom to biopsy, we would have biopsied and diagnosed 11/13 cases i.e. sensitivity of 85% but If we decide to biopsy those patients who had abnormal DRE and those who had low f/t PSA ratio, we could identify 13/13 carcinoma i.e. 100% sensitivity. Combining the f/t PSA ratio with total PSA, DRE and TRUS findings could help in reducing the number of unnecessary biopsies. 37 patients who were negative for malignancy having total PSA in the range of 5-20 ng/ml, normal DRE and TRUS findings, have been biopsied but with combination of total PSA in the range of 5-20 ng/ml, normal findings in digital rectal examination and TRUS and f/t PSA ratio more than 0.16 (cutoff), we could have avoided 16 biopsies which were unnecessary that means there was 43% reduction in unnecessary biopsies.