Distribution and secretory pathways of prostate specific antigen,alpha1-antichymotrypsin and prostate secretory granules in prostate cancers

Using 19 radical prostatectomy specimens, we studied the histological distribution of free prostate specific antigen (PSA), total PSA, alpha1-antichymotrypsin (ACT) and prostate secretory granules (PSG) in both normal and cancerous cells of the prostate. After glutaraldehyde fixation, numerous fine eosinophilic droplets of PSG could be found mainly in the apical portions of normal acinous epithelial cells, but was markedly decreased in cancer cells. With antibodies against free PSA, normal acinous cells were granularly positive in the apical portion of the epithelium, which corresponded to the PSG, whereas cancer cells were diffusely positive. With antibodies against ACT, normal duct cells and cancer cells were often positive, but few normal acinous cells were positive. Presumably, these findings indicate that free PSA is secreted into the lumen as PSG in normal glands, but not by the same pathway in cancers where free PSA appears to accumulate due to a decrease of PSG, then leak into the blood producing complexed PSA to some extent in the cytoplasm. One factor analysis of variance (ANOVA) on the correlation of tumor differentiation or Gleason score with serum values of total PSA, free PSA and a free/total PSA ratio demonstrated no significant links. Elucidation of secretory mechanisms should provide better comprehension of various PSA indices for prostate cancer screening.     

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer

Objective: As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. Methods: The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). Results: The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml²) than those with BPH (0.44 ± 0.21 ng/ml²) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. Conclusion: OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.     

前列腺特异性抗原EIA试剂盒的研制及应用

目的 建立可定量测定人血清中前列腺特异性抗原（ＰＳＡ）含量的夹心ＥＬＩＳＡ法,研制ＰＳＡ－ＥＩＡ检测试剂盒。方法 从健康男性精液中提取并纯化ＰＳＡ,分别免疫Ｂａｌｂ／ｃ小鼠和山羊制备特异性单克隆抗体和多克隆抗体,并以纯化的ＰＳＡ为标准品,建立可定量测定血清中ＰＳＡ含量的夹心ＥＬＩＳＡ法。在此基础上组装ＰＳＡ－ＥＩＡ试剂盒,对该试剂盒的特异性、灵敏度、精密度、正确性和稳定性等多项指标进行评价。应用该     

The utility of PSMA and PSA immunohistochemistry in the cytologic diagnosis of metastatic prostate carcinoma

The diagnosis of metastatic prostate carcinoma frequently requires the use of immunohistochemical adjuncts. Immunohistochemistry for prostate‐specific antigen (PSA) is commonly used for this purpose but can be of limited utility. Recently, prostate‐specific membrane antigen (PSMA) has been shown to be a promising marker for the identification of metastatic prostate carcinoma in surgical specimens. The utility of this marker has yet to be reported for cytology specimens. We sought to compare the sensitivities of PSMA and PSA immunohistochemistry and investigate the specificity of PSMA by utilizing cell block preparations from cytologic cases of metastatic prostate carcinoma (n = 19) and carcinomas of nonprostatic origin (n = 33). The sensitivity of PSMA immunohistochemistry was higher (16/19; 84%) in detecting metastatic prostate carcinomas than that of PSA immunohistochemistry (11/19; 58%). Strong, diffuse staining for PSMA was seen in 13 (81%) of 16 PSMA‐positive cases whereas strong, diffuse staining for PSA was observed in six (55%) of 11 PSA‐positive cases. Positivity for either PSMA or PSA was seen in 17 of 19 cases of metastatic prostate carcinoma for a combined sensitivity of 89%. PSMA immunohistochemistry was completely negative in 32 of 33 cytology cases of nonprostatic carcinomas. Therefore, the specificity of this marker was 97% in this study. In conclusion, our results indicate that PSMA is a highly sensitive and specific immunomarker for the detection of metastatic prostate carcinoma in cytology specimens. Diagn. Cytopathol. 2014;42:570–575. © 2013 Wiley Periodicals, Inc.     

Ductal (endometrioid) adenocarcinoma of the prostate: a clinicopathological study of 16 cases

Sixteen cases of ductal (endometrioid) carcinoma of the prostate are presented. The tumour presents in elderly men (age range 65–87 years) with haematuria or obstructive symptoms. Serum prostate specific antigen may be normal or raised. On cytoscopy, there is often an exophytic lesion in the region of the verumontanum. Histologically, two variants are recognized: papillary and cribriform, of which there were eight cases each. Eight cases consisted of pure ductal carcinoma and seven were mixed, containing a variable proportion of micro-acinar carcinoma.The associated micro-acinar carcinoma had a Gleason score of at least 5. One case of carcinosarcoma with a ductal epithelial component was also included. All cases displayed positive immunohistochemical staining for prostate specific antigen and prostatic acid phosphatase and but were negative for the basal cell marker MA903. The tumour responds well to orthodox micro-acinar carcinoma therapy and appears notably sensitive to hormonal manipulation. Follow-up of the mixed group is restricted to a maximum of 3 years. Of the eight pure cases, five patients are still alive with survival periods of 11, 8, 7, 3 and 1 years. Three patients died of intercurrent disease of which one patient survived 12 years, having received no treatment. This tumour, therefore, can be regarded as having a good prognosis.     

tPSA和cPSA对前列腺疾病诊断的临床价值

为了进一步探讨血清总前列腺特异性抗原(tPSA)和复合前列腺特异性抗原(cPSA)对前列腺疾病诊断的临床价值,用CLIA检测良性前列腺增生(BPH)组30例、前列腺癌(Pca)组30例患者和对照组45名血清tPSA和cPSA水平,比较各组间差异。结果表明:Pca组患者血清tPSA和cPSA水平较对照组及BPH组有显著性差异(P<0.01)。血清tPSA在低水平(4.0~10.0ng/mL),即“灰色区域”内,cPSA与tPSA对Pca组的阳性预测值比较有显著性差异(P<0.01)。Pca组联检tPSA cPSA的阳性率与单检tPSA或cPSA的阳性率比较有显著性差异(P<0.05)。本研究认为:tPSA、cPSA均是诊断与鉴别诊断Pca和BPH的重要指标。对Pca的诊断,血清tPSA在4.0~10.0ng/mL时,cPSA优于tPSA。联检tPSA cPSA可明显提高对早期Pca诊断的准确率。     

总PSA光激化学发光免疫分析法的建立

为了采用光激化学发光免疫分析技术建立快速定量检测总前列腺特异性抗原(tPSA)的方法。用两株配对的tPSA单克隆抗体,一株tPSA单克隆抗体包被受体微球,另一株tPSA单克隆抗体用生物素标记,与链霉亲合素的供体微球共同组成检测试剂。结果:自制tPSA试剂分析灵敏度为0.006ng/ml,线性测量范围为0.006～150ng/ml,分析内和分析间的精密度分别为3.90%～6.67%、4.71%～6.90%,与AFP、CA125、CA19-9和人白蛋白无明显交叉反应,136份临床血清样本用本试剂与罗氏化学发光试剂检测,其相关系数为0.979。提示:自制tPSA光激化学发光免疫分析试剂各项指标均能达到临床要求,有望替代国外同类产品。     

超声与血清t-PSA和f-PSA／t—PSA比值对前列腺癌诊断的价值

目的探讨血清总前列腺特异性抗原（t-PSA）、游离前列腺抗原／总前列腺抗原（f-PSA／t-PSA）比值与超声联检对前列腺癌（PCa）的诊断价值。方法将38例经手术和病理证实的PCa患者与45例前列腺增生（BPH）患者和40名正常人的t-PSA、f-PSA／t-PSA比值检测结果进行对比。并和超声联检结果进行分析。结果PCa患者血清t-PSA含量显著高于其它两组,差异有统计学意义（P〈0．01）。t-PSA和f-PSA／t-PSA比值作为单一指标应用于诊断PCa时,灵敏度分别为47．37％、73．68％,准确性分别为51．8l％、71．08％,与超声影像学三者联检,诊断PCa的灵敏度为94．73％,特异性为95．56％,准确性为95．18％。三者联检均高于其单检的敏感性,差异有统计学意义（P〈0．01）。结论t-PSA、t-PSA／foPSA是诊断PCa的较好指标。血清t-PSA、t-PSA／f—PSA比值和影像学联检可大大提高对PCa的诊断率,对PCa患者早期诊断、早期治疗和监控有重要作用。     

Prostate-specific antigen-positive extramammary Paget's disease--association with prostate cancer

Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5 of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease-two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens from the prostate revealed an immunoprofile which was very different from that of the primary skin lesion. In our study, no cases of EMPD with PSA positivity seem to represent an extension of an underlying prostatic adenocarcinoma. PSA positivity can be seen in cases of EMPD without associated adenocarcinoma of the prostate.     

前列腺增生症患者血清前列腺特异性抗原水平与前列腺炎关系的临床研究

目的探讨前列腺增生症患者血清中前列腺特异性抗原水平与前列腺炎的关系。方法120例门诊诊断为前列腺增生症的患者,其血清前列腺特异性抗原高于4.0ng/ml且合并前列腺炎;所有患者口服莫西沙星,治疗随访4周;根据治疗后血清前列腺特异性抗原水平及前列腺穿刺活检结果分为三组,观察比较各组治疗前后血清前列腺特异性抗原的水平及前列腺癌诊断阳性率。结果仅治疗后血清前列腺特异性抗原低于4.0ng/ml的一组在治疗前后的水平变化有统计学意义,其余两组均无统计学意义;治疗后前列腺癌诊断阳性率明显高于治疗前。结论对血清前列腺特异性抗原高于4.0ng/ml且合并前列腺炎的前列腺增生患者进行抗炎治疗,既可提高前列腺特异性抗原对前列癌早期诊断的特异性,又可使部分患者避免前列腺穿刺活检造成的痛苦和相关并发症。     

Prostate specific antigen and prostate specific acid phosphatase in adenocarcinoma of Skene's paraurethral glands and ducts

An autopsy case of adenocarcinoma of Skene's paraurethral gland co-incident with renal cell carcinoma is described. The adenocarcinoma showed distinct prostate specific antigen and prostate specific acid phosphatase pointing to the equivalence between the male prostate and Skene's paraurethral glands and ducts. Skene's gland are the homologue of the prostate in females and tumours arising from them are immunohistochemically similar to male prostate carcinoma.In the title and text the authors used the official term of Nomina Anatomica paraurethral (Skene's) glands and ducts. Nevertheless recently published data on cross-antigenicity between the male prostate and Skene's glands and the newly discovered exocrine and neuroendocrine parameters of the prostate homologue in the female, comparable with the male prostate (Zaviai 1987), support the use of the same term — the prostate — for prostatic tissue in both sexes (Zaviai 1987, Zaviai et al. 1985). The designations female prostate homologue or female prostate equivalent are a compromise between terms the female prostate and Skene's paraurethral glands.     

Immunohistochemistry of a prostate membrane specific protein during development and maturation of the human prostate

An antiserum against secretory vesicles from human seminal fluid (prostasomes) was used to study the localisation and distribution of the respective antigen(s) during prenatal development and pubertal maturation of the human prostate. The crude antiserum stained both secretory and membrane proteins in the adult prostate and other glands, such as pancreas and parotid gland. An immunoaffinity purified fraction from the antiserum selectively reacted with the apical plasma membrane of prostatic epithelium adluminal cells, recognizing a 100 kDa antigen (PMS). Even in the earliest stages of embryonic prostate specimens studied, the adluminal plasma membrane of the epithelial cells from developing glandular anlagen reacted strongly. The occurrence of PMS immunoreactivity in prostatic anlagen was directly correlated with lumen formation. As the antigen is an androgen-independently synthesised membrane protein of the prostate, it may possibly be used as a marker of cell polarity in the normal and pathologically altered prostate.     

Practice Patterns of Korean Urologists for Screening and Managing Prostate Cancer according to PSA Level

Purpose

There are still debates on the benefit of mass screening for prostate cancer (PCA) by prostate specific antigen (PSA) testing, and on systemized surveillance protocols according to PSA level. Furthermore, there is a paucity of literature on current practice patterns according to PSA level in the Korean urologic field. Here, we report the results of a nationwide, multicenter, retrospective chart-review study.

Materials and Methods

Overall 2122 Korean men (>40 years old, PSA >2.5 ng/mL) were included in our study (from 122 centers, in 2008). The primary endpoint was to analyze the rate of prostate biopsy according to PSA level. Secondary aims were to analyze the detection rate of PCA, the clinical features of patients, and the status of surveillance for PCA according to PSA level.

Results

The rate of prostate biopsy was 7.1%, 26.3%, 54.2%, and 64.3% according to PSA levels of 2.5-3.0, 3.0-4.0, 4.0-10.0, and >10.0 ng/mL, respectively, and the PCA detection rate was 16.0%, 22.2%, 20.2%, and 59.6%, respectively. At a PSA level >4.0 ng/mL, we found a lower incidence of prostate biopsy in local clinics than in general hospitals (21.6% vs. 66.2%, respectively). A significant proportion (16.6%) of patients exhibited high Gleason scores (≥8) even in the group with low PSA values (2.5-4.0 ng/mL).

Conclusion

We believe that the results from this nationwide study might provide an important database for the establishment of practical guidelines for the screening and management of PCA in Korean populations.     

Prostate hyperplasia in St Mary's Hospital Lacor: utility of prostate specific antigen in screening for prostate malignancy

IntroductionProstate cancer is the second commonest cancer in men worldwide. At present, every patient with lower urinary tract symptoms (LUTS) in St. Mary''s Hospital Lacor is undergoing prostate biopsy regardless of the prostate specific antigen (PSA) level. We sought to determine the association between PSA and malignant prostate histology.MethodsThis was a retrospective study. Data on age, PSA, prostate volume and prostate histology reported between Jan 2012 and Dec 2019 were retrieved from St. Mary''s Hospital Lacor archive and analyzed using STATA SE/13.0.ResultsRecords of 97 patients with LUTS was analyzed. The median (range) age of the patients was 71 (43–100) years. Median (range) of prostate volume was 91.8 (8.0–360.0) cc. Overall, PSA ranged from 0.21 to 399.2 ng/ml. Prostate histology showed 3.1% acinar adenocarcinoma, 24.7% adenocarcinoma and 72.2% benign prostatic hyperplasia. The median PSA amongst patients with malignant and non-malignant prostates were 15.8 ng/ml and 6.07 ng/ml respectively. Serum PSA level was significantly higher in patients with malignant prostate histology (Difference of mean= 9.7; p=0.001).ConclusionPatients with LUTS and PSA levels of 15ng/ml or more were more likely to have malignant prostate histology.     

血tPSA、cPSA、IGF-I联检对前列腺疾病诊断的临床价值

目的：探讨联检血清前列腺特异性抗原（tPSA）、复合前列腺特异性抗原（cPSA）、胰岛素样生长因子-I（IGF—I）含量及cPSA／tPSA比值对前列腺疾病诊断的临床价值。方法：分别采用磁微粒免疫化学发光法（ICLMA）和免疫放射分析（IRMA）对41例前列腺癌（PCa）、60例前列腺增生（BPH）患者和55例正常对照者进行tPSA、cPSA、IGF—I定量检测和计算cPSA／tPSA比值并比较分析。结果：PCa患者血清中tPSA、cPSA、IGF—I水平明显高于BPH组和正常对照组（P〈0．01）;BPH、PCa两组患者各项检测指标在“灰色区域”上分布差异有显著性（P〈0．01）;以tPSA〉4ng／ml、cPSA〉3．6ng／ml、IGF—I〉150和cPSA／tPSA〉0．74作为筛选PCa的临界值,其临床灵敏度、特异度、阳性预测值、阴性预测值分别为88．6％、84．9％、83．0％、90．0％。结论：联合使用tPSA、cPSA、cPSA／tPSA和IGF—I指标进行PCa的筛选,其临床诊断概率优于各单一指标,且对早期PCa的诊断和BPH的区别有重要的临床价值。     

Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen

Introduction

Ideally, there will be reproducible markers easily and non-invasively available to test for malignancy, or alternative procedures when there is no accurate marker available. For prostate cancer, one of the most common cancers in men, levels of prostate-specific antigen (PSA) lack specificity and sensitivity for the determination of malignancy when they fall within a range of values termed the ‘grey zone’.

Objective

To examine the predictive value of sialic acid in prostate neoplasms.

Study design

In our study of diagnostic accuracy we recruited 70 men complaining of urinary symptoms who presented in the urology department as outpatients or inpatients. All patients were checked with biopsy and pathology in order to relate benign and malignant lesions of the prostate to levels of sialic acid, a member of a family of acetylated products of neuraminic acid, which has so far proved to be a very sensitive and accurate marker of malignancy.

Results

The sialic acid level was found to be elevated in patients with prostate cancer (mean 75.06 ± 10.4 mg/dl) and reduced in patients with benign prostate hyperplasia (mean 57.086 ± 8.7 mg/dl) (p < 0.01); it had a sensitivity of 86% and specificity of 84% in diagnosing malignancy.

Conclusion

Sialic acid can be used as an adjunct in predicting prostate malignancy when PSA values fall in the grey zone.     

乳腺癌组织蛋白酶D和PSA表达与同侧腋淋巴结转移的关系

目的：探讨乳腺癌中组织蛋白酶Ｄ（ｃａｔｈｅｐｓｉｎＤ，ＣＤ）和前列腺特异性抗原（ＰＳＡ）的表达与同侧腋淋巴结转移的关系。方法：应用ＬＳＡＢ免疫组化法检测ＣＤ和ＰＳＡ在７８例乳腺癌中的表达，其中伴同侧腋淋巴结转移者３６例。结果：（１）７８例乳腺癌ＣＤ阳性表达率４１．０３％（３２／７８），ＰＳＡ阳性表达率４３．５％（３４／７８）；（２）同侧腋淋巴结转移组ＣＤ阳性表达率６９．４４％（２５／３６），无同侧腋淋巴结转移组ＣＤ阳性表达率１６．６７％（７／４２），差异有高度显著性（Ｐ＜０．０１）；（３）同侧腋淋巴结转移组ＰＳＡ阳性表达率２５．０％（９／３６），无同侧腋淋巴结转移组ＰＳＡ阳性表达率５９．５２％（２５／４２），差异有高度显著性（Ｐ＜０．０１）。结论：ＣＤ和ＰＳＡ的表达可作为乳腺癌预后检测的参考指标。ＣＤ表达阳性率与同侧腋淋巴结转移呈正相关，与预后负相关；而ＰＳＡ表达阳性率与同侧腋淋巴结转移呈负相关，与预后正相关     

NMR‐based evaluation of the metabolic profile and response to dichloroacetate of human prostate cancer cells

The aim of this study was to evaluate the metabolic profile of human prostate cancer cells that have different metastatic potential and to determine their response to dichloroacetate (DCA) using NMR technology. Two isogenic human prostate cancer cell lines, differing in their metastatic potential [LNCaP (poorly metastatic) and LNCaP‐LN3 (highly metastatic)], were studied. Metabolite ratios from NMR spectral integrals acquired at a field strength of 9.4 T using a 5‐mm broadband probe with an NMR‐compatible bioreactor were compared in the presence and absence of the pyruvate dehydrogenase kinase inhibitor DCA. Lactate dehydrogenase (LDH) isoenzymes were assessed by zymography. Following the treatment of cells with 50 mm DCA, there was a significant reduction in the lactate/choline, lactate/creatine, lactate/alanine and the combined lactate/(choline + creatine + alanine) ratios in LNCaP‐LN3 cells relative to LNCaP cells. No significant changes in metabolite ratios were found in LNCaP cells following DCA treatment. As expected, LDH zymography assays showed an absence of the LDH‐B subunit in LNCaP‐LN3 cells, whereas both LDH‐A and LDH‐B subunits were present in LNCaP cells. DCA was shown to significantly modify the metabolite ratios in highly metastatic LNCaP‐LN3 cells, but not in poorly metastatic LNCaP cells. This effect was probably related to the absence of the LDH‐B subunit in LNCaP‐LN3 cells, and could have a bearing on cancer treatment with DCA and related compounds. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.