前列腺增生组织中血管形成的研究

目的探讨血管形成在良性前列腺增生（ＢＰＨ）发病中作用及其与ｂＦＧＦ、ＰＣＮＡ之间的相关关系。方法应用免疫组化结合计算机图像分析方法检测第Ⅷ因子相关抗原、ｂＦＧＦ和ＰＣＮＡ在１８例正常前列腺（ＮＰ）和６２例ＢＰＨ中的表达及其相关关系。结果ＢＰＨ组织中微血管密度（ＭＶＤ）、ｂＦＧＦ和ＰＣＮＡ指数均显著高于ＮＰ;ＢＰＨ的ＭＶＤ与间质的面积百分比、ｂＦＧＦ表达和ＰＣＮＡ指数均呈正相关,而与上皮面积百分比负相关;ＮＰ的ＭＶＤ仅与间质的ＰＣＮＡ指数正相关。结论血管形成增多与ＢＰＨ的发生、发展有密切关系,尤其对间质细胞增殖、增生的作用更为显著,而ｂＦＧＦ异常表达可能是血管形成增多的主要原因之一。     

前列腺增生的组织形态及其PCNA表达的定量研究

目的探讨前列腺增生（ＢＰＨ）手术标本的组织形态及其细胞增殖状态的区域分布特征。方法应用ＨＥ染色和免疫组化染色结合计算机辅助图像分析方法，对２４例ＢＰＨ手术标本的三个区域中组织构成和增殖细胞核抗原（ＰＣＮＡ）表达进行定量分析。结果间质面积百分比和间质／上皮比值在尿道周围区、中间区和包膜下区中均依次递减（Ｐ＜０．０１），而上皮和腺腔面积百分比则依次递增（Ｐ＜０．０１）；三区间腺腔／上皮比值差异无显著性。尿道周围区ＰＣＮＡ指数高于其它两区（Ｐ＜０．０５）。结论ＢＰＨ的组织构成和细胞增殖状态存在着区域分布差异。     

前列腺增生组织中bFGFmRNA表达的意义

目的 探讨前列腺组织中碱性成纤维细胞生长因子（ｂＦＧＦ）基因和蛋白及基受体表达的意义。方法 应用原位分子杂交和免疫组化方法检测３８例前列腺增生（ＢＰＨ）组织和１０例正常前列腺（ＮＰ）组织中ｂＦＧＦｍＲＮＡ、ｂＦＧＦ和ＦＧＦＲ１表达。结果 前列腺间质细胞和上皮细胞中均见ｂＦＧＦｍＲＮＡ、ｂＦＧＦ和ＦＧＦＲ１阳性染色。ＢＰＨ间质细胞中三者表达显著高于ＮＰ组织,但ＢＰＨ与ＮＰ上皮细胞中三者表达无显著性。     

前列腺增生和癌变组织中碱性成纤维细胞生长因子的表达及 …

为了探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在前列腺癌组织中表达，分布民政部及临床意义，应用免疫组脂方法检测１４例正常前列腺（ＮＰ），５６你前列腺增生症（ＢＰＨ）和３３例前列腺癌（Ｐｃａ）组织中ｂＦＧＦ的分布和表达，结果显示：ＢＰＨ中ｂＦＧＦ阳性率为６４．３％，主要分布于间质细胞核，部分间质细胞浆，少数腺上皮细胞浆也见阳性染色，Ｐｃａ中ｂＦＧＦ阳性表达位于癌细胞浆，阳性率为８４．８％，但ｂＦＧＦ表达     

前列腺增生和癌变组织中碱性成纤维细胞生长因子的表达及其临床意义

为了探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在前列腺组织中表达、分布情况及临床意义，应用免疫组化方法检测１４例正常前列腺（ＮＰ）、５６例前列腺增生症（ＢＰＨ）和３３例前列腺癌（Ｐｃａ）组织中ｂＦＧＦ的分布和表达。结果显示：ＢＰＨ中ｂＦＧＦ阳性率为６４３％，主要分布于间质细胞核，部分间质细胞浆、少数腺上皮细胞浆也见阳性染色；Ｐｃａ中ｂＦＧＦ阳性表达位于癌细胞浆，阳性率为８４８％，但ｂＦＧＦ表达强度与Ｐｃａ的病理分级、临床分期无明显关系；正常前列腺组织中ｂＦＧＦ表达均为阴性，三者之间阳性率差异有显著意义，表明ｂＦＧＦ参与ＢＰＨ、Ｐｃａ发生过程。     

bFGF,EGFR和ABS在前列腺增生组织中的表达及其相前关系

目的：探讨ｂＦＧＦ、ＥＧＦＲ和ＡＢＳ在前列腺增生组织中的表达及其相关关系。方法：应用免疫组化方法。结果：三者在ＢＰＨ组织中均呈异常高表达。相关表达分析发现ｂＦＧＦ与ＥＧＦＲ在ＢＰＨ组织中正相关，而正常前列腺（ＮＰ）组织中无相关性；ＥＧＦＲ与ＡＢＳ在ＮＰ组织中表达呈负相关，ＢＰＨ组织中则无显著相关性；ｂＦＧＦ与ＡＢＳ在ＮＰ和ＢＰＨ组织中表达均无显著相关性。结论：ｂＦＧＦ、ＥＧＦＲ和ＡＢＳ在前列腺组织     

前列腺癌组织中细胞外基质的免疫组织化学研究

为探讨前列腺癌（ＰＣａ）细胞的转移机制，应用免疫组织化学ＡＢＣ法在良性前列腺增生（ＢＰＨ）及ＰＣａ组织中对基膜连接蛋白（ＬＮ），胶原Ⅳ型蛋白（ＣＯＬⅣ），纤维连接蛋白（ＦＮ）等细胞外基质（ＥＣＭ）蛋白的表达进行检测，结果ＢＰＨ组织中基底膜部位ＬＮ，ＣＯＬⅣ及ＦＮ的染色呈连续线状分布，ＰＣａ组组织基底膜部位ＬＮ，ＣＯＬⅣ及ＦＮ的阳性染色呈碎片状或断线状分布。ＣＯＬⅣ在ＢＰＨ与ＰＣａ组织中的强阳性率无显著性差异（Ｐ＞０．０５）。结果提示ＥＣＭ在ＰＣａ组织中基底膜部位的明显缺失（非连续线状分布）可能是肿瘤转移的重要因素。     

膀胱癌碱性成纤维细胞生长因子表达的意义及其与增殖细胞核 …

目的 探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在膀胱癌中表达及其作用以及与增殖细胞核抗原（ＰＣ－ＮＡ）之间的关系。方法 应用免疫组化方法检测胶胱癌和正常膀胱组织 两者表达。结果 膀胱癌中ｂＦＧＦ表达显著高于正常组织，而且与肿瘤的病理分期分级、复发及大小之间有密切关系，但与ＰＣＮＡ表达之间无显著相关关系。结论 ｂＦＧＦ异常表达在膀胱癌发生发展过程中起重要作用，而且可以作为肿瘤生物学行为和复发的预示标记     

BPH组织中bFGF、bFGFR表达及其对前列腺组成的影响

对６例正常前列腺和３０例前列腺增生（ＢＰＨ）患者组织中成纤维细胞生长因子ｂＦＧＦ、ｂＦＧＦＲ表达以及前列腺组成成分的改变进行定量分析。ｂＦＧＦ和ｂＦＧＦＲ在ＢＰＨ组织中表达水平（４８．３２±１４．６３，２１．６７±１１．７６）明显高于正常前列腺（２５．１６±１０．８７，４．３５±３．４９），其表达水平与前列腺间质成分增生呈正相关。本研究表明ｂＦＧＦ以及受体在ＢＰＨ形成中可能起重要的作用。     

胰岛素样生长因子－I mRNA在前列腺组织中的表达

对１５例良性前列腺增生（ＢＰＨ）和１２例正常前列腺组织标本中胰岛素样生长因子－Ｉ－（ＩＧＦ－Ｉ）ｍＲＮＡ的表达情况进行了研究。ＲＴ－ＰＣＲ的方法可自所有标本中检出ＩＧＦ－ＩｍＲＮＡ的表达，并用电泳和Ｓｏｕｔｈｅｒｎ杂交证实了结果的可靠性。原位杂交表明１３／１５的ＢＰＨ和９／１２的正常前列腺标本中有ＩＧＦ－ＩｍＲＮＡ表达，ＩＧＦ－Ｉ在上皮的表达强于间质，尤以基底细胞表达最明显。ＩＧＦ－ＩｍＲＮＡ在ＢＰＨ组织中的量多于正常前列腺。     

Regional distribution of epidermal growth factor,testosterone and dihydrotestosterone in benign prostatic hyperplasia tissue

In benign prostatic hyperplasia (BPH), basic fibroblast growth factor (bFGF) is found to have a regional distribution, with concentrations in the periurethral zone (where the primitive fibrostromal nodule originates) higher than those of the peripheral subcapsular zone. The aim of the present investigation was to verify whether androgens and epidermal growth factor (EGF) are uniformly distributed from the periurethral to the peripheral zone or whether they show regional differences. Tissue samples, removed by transvesical resection from nine untreated BPH patients, sectioned in periurethral, subcapsular, and intermediate zones, were examined. In the periurethral zone, dihydrotestosterone (DHT), testosterone, and EGF, determined by radioimmunoassay (RIA) techniques after purification on Celite microcolumns and Sep-pak C18 cartridge, showed values significantly higher (mean ± SD: 1121±482 pg, 250±129 pg, and 6.89±3.28 ng/mg DNA, respectively;P<0.01) than those of the subcapsular zone (489±190 pg, 114±70 pg, and 3.40±1.90 ng/mg DNA, respectively). A positive linear correlation between EGF, testosterone, and DHT was also observed. The regional distribution of EGF, testosterone, and DHT was similar to that found for bFGF: the highest levels of these factors in the periurethral region allow us to hypothesize on their possible involvement in the rewakening of mesenchymal tissue, leading to the formation of the primitive fibrostromal nodule and then to BPH development.     

Can the intraprostatic concentration of epidermal growth factor influence the variance of serum prostate specific antigen levels in patients with benign prostatic hyperplasia?

PURPOSE: Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels. MATERIALS AND METHODS: A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue. RESULTS: In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively). CONCLUSIONS: To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.     

良性前列腺增生细胞因子变化的研究

目的　探讨与细胞增生有关的细胞因子与BPH发生的相关性。方法　人前列腺分对照组 (正常前列腺 )和实验组 (良性前列腺增生 )。常规组织学染色观察组织形态的变化 ,免疫组织化学方法观察bFGF ,VEGF和EGFR在BPH中的改变。结果　BPH的病理变化呈多类型化。BPH的组织中bFGF和VEGF在间质中明显增加 ;EGFR在腺上皮和间质细胞中都增加明显。结论　在BPH的组织异常增殖中 ,间质的增殖可能与bFGF和VEGF的分泌增多关系密切 ,而EGFR与间质和腺上皮的异常增殖均有关。     

Autoradiographic localization of alpha 1-adrenoceptors in human prostate: special reference to zonal difference.

Using autoradiography, localization of alpha 1-adrenoceptor in human prostate was examined with particular reference to zonal difference. Prostatic tissues were obtained from total cystoprostatectomy specimens of six male bladder tumor patients. Peripheral zone (PZ), central zone (CZ) and preprostatic region which contained preprostatic sphincter and periurethral gland were dissected from the tissues. [125I]-HEAT was used as radioligand for autoradiography. Autoradiographic distribution of alpha 1-adrenoceptor was quantitated by grain counting using a light microscope equipped with a micrometer. Specific binding was demonstrated predominantly in fibromuscular stroma of PZ, fibromuscular stroma of CZ and preprostatic sphincter. No specific binding was demonstrated in glandular epithelium of PZ and periurethral gland. Glandular epithelium of CZ showed a few specific bindings. Among fibromuscular portion, specific bindings in both CZ and preprostatic sphincter were significantly higher than in PZ. Specific binding in glandular epithelium of CZ was significantly less than in fibromuscular stroma of PZ. These results show that the human prostate has a zonal difference in the distribution of alpha 1-adrenoceptors, probably reflecting some functional difference in these regions.     

Benign prostatic hyperplasia and growth factors.

A great deal of work has been accomplished in the attempt to determine the cause of benign prostatic hyperplasia (BPH). Early work by morphologists suggests that BPH starts as a stromal disease and that the hyperplastic stroma secretes a substance that stimulates the growth of epithelial cells. The quantitative morphometric data also suggest that BPH is primarily a stromal disease. Experimental embryology data have shown that the basic fibroblast growth factor, bFGF, is involved in early embryogenesis and is the primary inducer of mesodermal tissue. Work in mouse embryos has shown that a powerful inducer for prostatic epithelial growth is elaborated by the urogenital mesenchyme. Both of these findings fit the hypothesis that stromal hyperplasia may be initiated by a growth factor and that a second growth factor stimulates epithelial growth. Work in our laboratory has established that bFGF is the primary growth factor present in human BPH. We have also found that bFGF is synthesized by prostate fibroblasts and bFGF may be in higher concentration in the periurethral tissues of BPH. At this time, no definite link between growth factors and hyperplastic growth of the prostate has been established. However, circumstantial evidence has lead us to formulate several hypothesis regarding the role of growth factors in BPH. Hopefully, these hypothesis will be of some assistance in guiding future work on growth factors and BPH.     

前列腺移行带及外周带细胞增殖和凋亡的研究

目的:研究前列腺不同区带间细胞的增殖和凋亡,并比较其差异。方法:应用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测17例正常前列腺移行带和外周带、20例良性前列腺增生(BPH)移行带上皮细胞凋亡率,免疫组化法检测细胞增殖核抗原(PCNA)及Bcl-2表达。RT-PCR法半定量验证Bcl-2 mRNA表达。结果:①正常前列腺移行带上皮细胞凋亡率和增殖率均显著低于外周带[(13.7±4.32%)vs(20.9±6.44)%和(14.6±4.34)%vs(25.6±6.35)%,P<0.01],增生的移行带上皮细胞凋亡减少,同时细胞增殖增加。②正常前列腺外周带上皮细胞Bcl-2表达率低于移行带,后者又显著低于BPH移行带(P<0.01)。增生的移行带中Bcl-2表达率与上皮细胞凋亡率呈显著负相关(rs=-0.867,P<0.01)。结论:移行带和外周带存在细胞增殖和凋亡率差异。增生的移行带上皮细胞凋亡减少,同时细胞增殖增加,这可能是BPH的重要病理基础。Bcl-2在移行带高表达参与了BPH病理过程。     

Immunocytochemical localization of estrogen receptors in spontaneous and experimentally induced canine benign prostatic hyperplasia

Estrogens are believed to play a critical role in the etiology of canine benign prostatic hyperplasia (BPH); however, the mechanism has not been elucidated. To gain insight into this problem, we investigated the immunocytochemical localization of estrogen receptors (ER) in normal prostates, spontaneous BPH, and experimentally induced BPH by using a monoclonal ER antibody (H222). In all canine prostates the majority of ER was localized in nuclei of the same histological components: (1) transitional epithelium and subjacent stroma of the prostatic urethra, (2) periurethral prostatic ductal epithelium, and (3) prostatic stroma. ER content in the stroma was highest in the periurethral region of the prostate. Among the different groups of dogs, differences in ER location were seen only in the glandular epithelium. No ER was found in the glandular epithelium of normal prostates of young untreated dogs. In striking contrast, glandular epithelium of spontaneous BPH contained specific nuclear ER staining, though this staining was heterogeneous and was observed in only a minority (less than 10%) of the acinar epithelial cells. ER-positive acini in BPH were located predominantly in the periurethral region. These data demonstrate anatomical and biochemical heterogeneity of prostatic components and indicate that the estrogen sensitivity of prostatic cells is heterogeneous. If estrogen does play a role in BPH, it appears to act selectively rather than uniformly throughout the prostate. We reasoned that if glandular epithelial ER are involved in the development of spontaneous BPH, one might expect to find the same location of ER in BPH that was induced experimentally by specific types of treatment with androgens +/- estradiol. However, among hormone-treated dogs the presence of ER-positive prostatic glandular epithelium varied with the type of hormonal treatment but did not correlate with the experimental induction of glandular BPH. Some treatment groups with induced BPH had ER-positive prostatic glandular epithelial nuclei (with the same extent and pattern of ER localization as in spontaneous BPH); however, other treatment groups with induced BPH had ER-negative glandular epithelium. These data indicate either that glandular epithelial ER may not be involved in the pathogenesis of canine BPH or that there may be different types of BPH that have different etiologies. Possible mechanisms by which estrogen may affect the canine prostate are discussed in light of these new data on ER location.