Relationship of prostatic acid phosphatase localization in human prostate by a monoclonal antibody with the Gleason grading system

Prostatic acid phosphatase (PAP) was localized in human prostate with a monoclonal antibody prepared against PAP isoenzyme II to determine patterns of its expression in normal, hyperplastic (BPH), and cancerous glands. The monoclonal antibody reacted with both isoenzymes II and IV in immunoblot studies. Formalin-fixed, paraffin-embedded tissue was used from patients who had not been treated with hormones or chemotherapy. In normal glands and BPH, there was marked variation in the intensity of PAP staining in morphologically otherwise similar epithelial cells. There was similar heterogeneity of staining in the adenocarcinomas. Rough quantification of the intensity patterns in the clinical groups indicated a slight shift to more intense staining in BPH and well-differentiated carcinomas but a progressive decline in the PAP staining in the moderately and poorly differentiated tumors. This decrease in intracellular staining with decreasing differentiation is not inconsistent with the clinical observation that serum levels of acid phosphatase generally increase with higher grade and disseminated tumors, since the enzyme is simply more accessible to the circulatory system in those cases. The same decrease may explain the few disseminated tumors that are not associated with elevated serum levels.     

Effects of prolactin on explant cultures of rat ventral prostate: Morphological and immunohistochemical study

Specimens derived from rat ventral prostate were cultured by an explant culture technique using differents concentrations of ovine prolactin. Sacrified explants embedded on paraffin were sectioned for morphologic and immunocytochemical studies using antibodies against prostatic acid phosphatase, prostatic specific antigen, and wide-spectrum monoclonal keratin. Prolactin significantly stimulated the growth of these cells in the concentration range of 1 × 10^?2 ui/ml, but was inhibitory at a concentration of 1 and 0.1 ui/ml. The 1 × 10^?3 and 1 × 10^?4 ui/ml prolactin concentrations demonstrated the preservation of a glandular epithelium with a columnar shape, similar to the normal appearance of ventral prostate from rats. © 1993 Wiley-Liss, Inc.     

Two-dimensional characterization of prostatic acid phosphatase, prostatic specific antigen and prostate binding protein in expressed prostatic fluid

Specimens of pooled prostatic fluid, collected by rectal massage from men under 50 years of age with no apparent prostatic disorders, were subjected to two-dimensional gel electrophoresis to study the composition of its proteins. In a preliminary study, a total of 57 major protein groups were detected. In the present study, we attempted to identify, in the two-dimensional gels, those that are related to prostate-associated proteins, i.e., prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), and prostate binding protein (PBP). Individual proteins were recognized by the procedure of Western Blot using specific antisera with peroxidase-antiperoxidase as the staining reagent. Each protein spot in the two-dimensional gel was expressed, along the abscissa, by its isoelectric point (pI) and, along the ordinate, by the molecular weight (MW). PAP consisted of a train of more than ten protein spots that occupied an area in the gel from pI 7.0, MW 45,000 to pI 6.0, MW 50,000. Four protein spots with a MW of 34,000 and a pI range of 8.2-8.8 were identified as PSA. PBP was observed as having three protein spots that were located at pI 5.6-6.6 with a single MW of 15,000. For PAP and PSA, additional protein spots with lower MWs also stained positively with the specific antisera, suggestive of the presence of degradative products of these proteins. Following the removal of the serum-related proteins by an extensive absorption with anti-human serum antibody by affinity chromatography, the prostatic fluid contained 27 major groups of non-serum proteins. These non-serum proteins in the prostatic fluid included PAP, PSA, PBP, and their related smaller molecular species. These results indicate that the prostatic fluid contains PAP, PSA, PBP and that their presence and the patterns of their distribution in the two-dimensional gels should be considered as the characteristic property of the prostatic secretions.     

A clinical and immunohistochemical study of papillary adenocarcinoma of the prostate

Clinical and immunohistochemical studies were conducted to evaluate prostatic papillary adenocarcinoma and prostatic papillary hyperplasia. Subjects consisted of 5 cases of papillary adenocarcinoma and 2 cases of papillary hyperplasia. There is no conclusive clinical factor for preoperative diagnosis, but we attach importance to endoscopic findings. PSA, PAP, high molecular weight cytokeratin, and PCNA were evaluated immunohistochemically. PSA became positive in every instance but one—a case of papillary adenocarcinoma which became ±. PAP was + in all cases, except for 1 case of papillary adenocarcinoma. Basal cells were positive for high molecular weight cytokeratin in 2 cases of papillary hyperplasia but were missing in papillary adenocarcinoma. Although PCNA was free from positive nuclei in papillary hyperplasia, positive nuclei were found in all cases of papillary adenocarcinoma. Considering these immunohistochemical results, papillary adenocarcinoma can be said to originate in the glandular epithelium of the prostate, as does ordinary prostatic carcinoma.     

Immunoelectron microscopic demonstration of prostatic acid phosphatase in human hyperplastic prostate

Immunoelectron microscopic studies were done on prostatic tissues obtained from patients with benign hyperplasia. Rabbit IgG-peroxidase conjugate against purified human prostatic acid phosphatase band 2 (HPAP-2) was used for studies. Under the light microscope, the columnar secretory epithelia of prostatic glands showed different intensity and distribution of immunostaining whereas the basal cells were unstained. Under the electron microscope, the secretory epithelial cells often showed electron-dense reaction product in the Golgi apparatus and secretory vesicles and vacuoles, and only sparingly in the cisternae of nuclear envelope and rough ER. Sometimes, fusion of secretory vacuolar membrane and plasma membrane and discharge of the vacuolar contents into the extracellular space were noted. The surfaces of microvilli at the apical portion of the columnar epithelia and the lumen of the glandular acini always showed reaction product. These findings suggest that HPAP-2 may be synthesized in the rough ER and transported to the Golgi apparatus where it is concentrated and transferred to the secretory vesicles and vacuoles. HPAP-2 is finally discharged into the extracellular spaces through exocytosis, a secretory mechanism similar to that of other secretory proteins.     

Expression of NEU/HER-2 oncoprotein (p185neu) in prostate tumors: An immunohistochemical study

The expression of the neu oncogene product was investigated immunohistochemically in 36 cases of benign prostatic hyperplasia (BPH) and seven cases of adenocarcinoma of prostate (CaP). c-neu oncogene encodes a transmembrane growth factor receptor that has partial structural homology with EGF receptor, and is overexpressed and amplified in a number of human tumors, specially, breast cancers. Using a monoclonal antibody, AB-3, which recognizes -COOH-terminal of neu oncoprotein, we have analyzed immunohistochemically the expression of this protein in buffered formalin and Zamboni fluid-fixed surgically removed tissues. Focal patchy and/or diffused cytoplasmic staining of varying intensity was observed in 34 of 36 BPH cases. Four cases showed cell membrane staining as well (4/36 = 11%). All seven cases of adenocarcinomas had moderate to strong c-neu immunoreactivity, and two gave a distinct cell membrane-positive reaction (100%). The available data indicate that prostatic tumors as well as a high percentage of prostatic hyperplasia tissues express c-neu protein; however, its role in cellular proliferation needs further study. © 1993 Wiley-Liss, Inc.     

Adenocarcinoma of the canine prostate: immunohistochemical examination for secretory antigens

Thirty-one canine adenocarcinomas of prostatic origin were examined immunohistochemically with antibodies generated against three prostate-specific antigens by using a peroxidase-antiperoxidase technique. Primary antibodies included two generated with human prostatic antigens (PSA, PSAP) and one generated with a canine prostatic antigen (CPSP). Eight of 31 adenocarcinomas were positive with CPSP, two were positive with PSA, and three were PSAP positive. Normal and hyperplastic canine prostatic epithelium was strongly positive with all three markers. These results contrast with those in human studies in which PSA and PSAP stain normal and neoplastic epithelium with comparable intensity in all but the most anaplastic tumors.     

双抗体夹心一步法检测前列腺特异抗原及应用的评价

用聚乙二醇、葡聚糖凝胶（ＰＥＧ、Ｓｅｐｈａｄｅｘ）两步法提取精浆前列腺特异抗原（ＰＳＡ），建立了一步检测血清ＰＳＡ的ＥＬＩＳＡ法及正常参考值范围。经５８例临床标本及９５例正常男性血清ＰＳＡ测定，对前列腺癌诊断的敏感性和特异性分别为１００％和９４．２％；６０岁以下和６０岁以上的男性血清ＰＳＡ临界值分别为３．４μｇ／Ｌ和４．６μｇ／Ｌ。表明年龄因素对ＰＳＡ测定有较大影响，在判断测定结果时必须加以考虑。     

TRPC6在人良性与恶性前列腺组织中的表达

观察瞬时受体电位通道C6（TRPC6）在人良性与恶性前列腺组织及前列腺癌细胞系中的表达,进一步探讨TRPC6的表达与前列腺癌分期、分级及激素依赖性的关系。利用免疫组织化学技术,检测发现45．0％的前列腺增生和86．6％的前列腺癌病例表达TRPC6,两者比较有显著性差异沪〈0．01）。TRPC6的表达与前列腺癌分级和前列腺外转移有关（P〈0．01）。前列腺癌分期增高,TRPC6表达增多,但在T2、T3和DT4期肿瘤病例中,TRPC6表达无显著差异。此外TRPC6在激素依赖性前列腺癌与激素非依赖性前列腺癌中的表达也无显著差异。应用RT-PCR及Westernblot,检测到TRPC6在前列腺癌细胞系中的表达。本研究发现,TRPC6在良性与恶性前列腺组织及前列腺癌细胞系中表达。TRPC6的表达与前列腺癌的组织分级、Gleason评分及前列腺外转移有关。     

前列腺组织中睾酮含量状态与前列腺生理和增生的关系

目的：检测前列腺组织中总睾酮、结合睾酮和游离睾酮的含量，并分析其与前列腺生理和组织增生的关系。方法：14例相对年轻正常前列腺组织、22例良性前列腺增生(BPH)组织和ll例相应年龄段前列腺对照组织，制备组织脑浆和胞核提取液，乙醚萃取分离游离和结合睾酮，采用^125I标记睾酮放免试剂盒测定睾酮的含量。结果：前列腺组织中睾酮存在结合和游离2种状态，结合态为多，约占2/3；3组比较，总睾酮、游离和结合睾酮含量无显著差异。结论：前列腺组织中睾酮存在游离和结合二种状态，共同维持局部高水平的总睾酮含量，并且随年龄增长而保持稳定，有利于睾酮在前列腺生理和组织增生过程中的作用。     

酒精对大鼠前列腺抗氧化酶活性和脂质过氧化的影响

目的 探讨酒精对大鼠前列腺组织抗氧化酶活性和脂质过氧化水平的影响。方法 40只成年健康SD雄性大鼠随机均分为对照组、低剂量组、中剂量组和高剂量组，分别用50．0％、25．0％、12．5％的乙醇溶液和蒸馏水按10．0ml／kg每晚灌胃1次持续60d后，观察酒精毒染模型大鼠前列腺组织的形态结构的变化；用化学比色法测定前列腺组织中超氧化物岐化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）和前列腺酸性磷酸酶（PAP）的水平。结果 随着酒精剂量的增加，SOD、CAT、GSH-Px活力和PAP含量呈先升高后下降的趋势，MDA含量和前列腺相对重量分别呈现上升和下降趋势，前列腺组织馆牛棼缩。结论 长期过量饮洒可导致大鼠前列腺绸织结构和功能异常，氧化应激在其中发挥了重要作用。     

Effect of culture conditions on androgen sensitivity of the human prostatic cancer cell line LNCaP

Several effects of androgens on LNCaP-FGC prostate tumor cells showed a biphasic pattern. Stimulation of growth and inhibition of secretion of prostatic acid phosphatase (PAP) was observed at low androgen concentrations (below 1 nM of the synthetic androgen R1881), and inhibition of growth and stimulation of PAP secretion was observed at higher concentrations. In contrast, prostate specific antigen (PSA) secretion did not show this biphasic response pattern. Comparable effects were found for two sublines of the LNCaP-FGC cells: an early (passage 20, androgen-dependent) and relatively late (passage 70, androgen-sensitive) passage of the cells. Culturing of both sublines in the presence of a high concentration of androgens (10 nM R1881) resulted initially in a decrease in growth rate, but the cells started to proliferate within 3 weeks. These cells became less sensitive to androgens, lost their biphasic response pattern, and showed reduced androgen receptor levels. Three weeks after removal of the excess of androgens, the passage 70 cells regained a biphasic growth response to androgens. Culture in medium without steroids but with EGF resulted in a decrease of both androgen sensitivity and androgen receptor level. In conclusion, rapid changes of the androgen sensitivity and receptor level of the LNCaP cells occurred under the influence of culture conditions. These changes were partly reversible and, therefore, were most likely due to adaptation of the cells. © 1993 Wiley-Liss, Inc.     

Effects of short-term high-dose testosterone propionate administration on medium molecular-weight proteins of human seminal plasma

Summary. Effects of short-term high-dose testosterone propionate treatment on medium molecular-weight proteins (lactoferrin, albumin, prostatic acid phosphatase, prostate specific antigen) and on zinc and fructose levels were investigated in the seminal plasma of seven normal volunteers. A significant reduction in levels of prostatic-acid phosphatase, zinc and, to a lesser degree, prostate-specific antigen, lactoferrin and fructose was observed on the 14th day of androgen treatment, concomitantly with the maximal increase in free androgen-circulating levels. The data obtained suggest that testosterone administration may induce a reduction in the sex accessory-gland secretion. Indeed, this effect tends to disappear with withdrawal of hormone treatment. Therefore, the authors suggest a close follow-up of prostatic and vesicular function during the long-term high-dose testosterone intake, used frequently as anabolic treatment by athletes and body builders.     

前列腺癌组织中人软骨糖蛋白-39的表达及意义

目的 探讨人软骨糖蛋白-39在前列腺癌组织中的表达及临床意义.方法 应用免疫组织化学法检测70例前列腺癌组织、30例前列腺增生组织及10例正常前列腺组织中人软骨糖蛋白-39的表达水平.结果 前列腺癌组人软骨糖蛋白-39表达明显高于前列腺增生组和正常前列腺组,差异有统计学意义(P＜0.01)；人软骨糖蛋白-39的表达在前列腺癌不同病理分级及临床分期中表达不同；生存分析显示人软骨糖蛋白-39阳性患者生存时间短于阴性患者(P＜0.05).结论 人软骨糖蛋白-39的表达与前列腺癌发生、发展及预后有密切的关系,检测前列腺组织中人软骨糖蛋白-39的表达有助于预后的评估.     

Detection of prostate cancer in males with prostatism

The present study was designed to compare the prostate cancer detection rate, sensitivity, specificity, and positive predictive value of digital rectal examination (DRE) and serum prostatic specific antigen (PSA) in a consecutive cohort of males presenting to a single institution with clinically significant prostatism. The study population was comprised of 224 consecutive males with clinically significant prostatism referred to the Prostate Center at the Medical College of Wisconsin between June 1990 and December 1991. Subjects were considered to have clinically significant prostatism if they elected to pursue medical or surgical therapy following exclusion of carcinoma of the prostate. The initial examination consisted of a Boyarsky symptom score assessment, DRE, uroflowmetry, postvoid residual determination, serum PSA level, and transrectal prostatic ultrasonography. Subjects with an abnormality on DRE or serum PSA > 4 ng/dl were advised to undergo transrectal prostatic biopsy. Of the 224 subjects, 40 (17.9%) had an abnormal DRE and 57 (25.4%) had an elevated serum PSA > 4 ng/dl. The overall detection rate of prostate cancer in the study population was 6.7%. The prostate cancer detection rates for PSA alone and DRE alone were 5.8% and 5.3%, respectively. The sensitivity, specificity, and positive predictive values of PSA alone were 86.7%, 80.9%, and 25.0% and of DRE alone 80.0%, 86.3%, and 30.0%, respectively. Receiver operator characteristic (ROC) curves were constructed for the entire study population in order to compare the screening measures serum PSA and PSA density. The area under the curves was 0.88 for both tests, indicating that these screening tests for prostate cancer were not significantly different. The present study demonstrated that males with clinically significant prostatism represent a high risk cohort for detecting prostate cancer. DRE and PSA are equally effective measures for detecting prostate cancer. PSA density does not offer any advantage over serum PSA in screening for prostate cancer, except in the subset of patients with a normal DRE and serum PSA levels between 4.0 and 9.9 ng/dl. © 1994 Wiley-Liss, Inc.