EGFR和ABS在前列腺增生和癌变组织中的表达及意义

为探讨前列腺增生和前列腺癌的病因及发病机制，应用免疫组织化学ＳＰ法检测了１４例正常前列腺、６０例前殓腺增生和３３例前列腺癌组织中表达生长因子受体和雄激素结合位点的表达。结果显示，前列腺增生和前列腺癌组织中ＥＣＦＲ阳性表达率明显高于正常组织；前列腺癌中ＡＢＳ的阳必明显高于增生和正常组织，而增生组织中，ＡＢＳ强阳性率又明显高于正常组织。ＥＧＦＲ表达与肿瘤病理分级呈正相关，而与ＡＢＳ表达无相关。ＥＧＦＲ     

前列腺病变组织中嗜银蛋白和增殖细胞核抗原表达及意义

为探讨早期诊前列腺良，恶性病变的生物学行为指标，采用银染色和免疫组织化学染色法对７４例前列腺良，恶性病变组织中细胞核仁组成区嗜银蛋白和增殖细胞核抗原进行检测。结果前列腺癌组织中ＡｇＮＯＲ和ＰＣＮＡ的表达明显高于前列腺非典型增生，前列腺增生症和前列腺炎，其表达依次呈递减趋势，前列腺非典型增生的ＡｇＮＯＲ和ＰＣＲＮＡ计是于前列腺癌与前列一症之间，表明前列腺非曲型增生具有潜在的恶可能。前列腺癌中ＡｇＮＯ     

前列腺癌及前列腺增生组织EGF,EGFr表达的差异及意义

对前列腺增生症及前列腺癌中ＥＧＦ、ＥＧＦｒ表达进行了观察。７５％ＢＰＨ表达ＥＧＦ，５８％ＢＰＨ有ＥＧＦｒ阳性染色。２７例前列腺癌中１３例（４８％）ＥＧＦ阳性，仅４例（１５％）表达ＥＧＦｒ。ＥＧＦｒ在前列腺癌中低水平表达可能与原癌基因Ｃ－ｅｒｂＢ－１表达调控有关。本研究未能发现ＥＧＦｒ表达与肿瘤组织学类型及预后的关系。因此认为对ＥＧＦｒ在肿瘤组织中表达的临床意义的解释应慎重。     

前列腺癌,非典型增生的AgNOR数量变化的初步研究

对４３例前列腺癌、３０例前列腺非典型增生及１９例良性前列腺增生症的石蜡包埋标本，应用核仁组成区染色技术系统地观察了核仁组成区（ＡｇＮＯＲ）的数量变化。结果显示：前列腺癌平均ＡｇＮＯＲ计数显著高于良性前列腺增生症者；前列腺非典型增生的ＡｇＮＯＲ计数介于良性增生症与癌组织之间，说明前列腺非典型增生具有潜在的恶性病变。前列腺癌平均ＡｇＮＯＲｓ计数与组织学分级关系密切，随肿瘤组织的分级增高而增高，不同的组织分级之间其平均ＡｇＮＯＲ计数有显著的差异，提示ＡｇＮＯＲ颗粒与前列腺癌的分化程度有关。     

表皮生长因子受体和转化生长因子—α在前列腺癌表达中的临？…

目的：探讨表皮生长因子本（ＥＧＦＲ）和转化生长因子－α（ＴＧＦα）在前列腺癌（ＰＣａ）中表达的临床意义。方法；采用免疫组化法检测４３例ＰＣａ组织和５例正常前列组织中ＥＧＦＲ和ＴＧＦα的表达。结果：正常前列腺组织中ＥＧＦＲ和ＴＧＦα和ＴＧＦα分别表达在上皮细胞和基质中，ＥＧＦＲ和ＴＧＦα在ＰＣａ细胞上的共同表达率为５５．８％，二者密切相关，并与ＰＣａ分期有关；此类患者的生存时间明显短于ＥＧＦＲ和ＴＧ     

表皮生长因子及其受体在前列腺中的作用

表皮生长因子（ＥＧＦ）及其受体（ＥＧＦＲ）在前列腺的正常发育和病理性生长过程中的作用已成为近年来人们关注的焦点之一。本文综述了ＥＧＦ和ＥＧＦＲ的一般性生物学特性以及在正常前列腺、前列腺增生和前列腺癌中的生物学作用及其与性激素和其他相关生长因子之间的相互关系。     

表皮生长因子及其受体在前列腺中的作用

表皮生长因子（ＥＧＦ）及其受体（ＥＧＦＲ）在前列腺的正常发育和病理性生长过程中的作用己成为近年来人们关注的焦点之一。本文综述了ＥＧＦ和ＥＧＦＲ的一般性生物学特性以及在正常前列腺、前列腺增生和前列腺癌中的生物学作用及其与性激素和其他相关生长因子之间的相互关系。     

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     

前列腺增生症各区细胞增殖与凋亡特征的研究

目的 探讨良性前列腺增生症（ＢＰＨ）各区细胞增殖和凋亡特征及其与ＢＰＨ发病的关系。方法 采用流式细胞术对３３例ＢＰＨ病人前列腺各区细胞表皮生长因子（ＥＧＦ）,表皮生长因子受体（ＥＧＦ－Ｒ）,碱性纤维细胞生长因子和转化生长因子－β１（ＴＧＦ－β１）表达,细胞ＤＮＡ含量和细胞凋亡情况进行定量对比分析。结果 ＥＧＦ和ＥＧＦ－Ｒ的标记率和表达量在移行区（ＴＺ）明显高于周边区（ＰＺ）和中央区（ＣＺ）。     

前列腺增生组织HLA—DR抗原分布及意义探讨

对正常前列腺、慢性前列腺炎及前列腺增生症中ＨＬＡ－ＤＲ抗原的分布进行观察。结果表明：正常及前列腺炎的腺上皮均无ＨＬＡ－ＤＲ表达，但８７．５％前列腺增生症的腺上皮异常表面ＨＬＡ－ＤＲ抗原。腺上皮ＨＬＡ－ＤＲ表达的强弱，与前列腺组织损伤变性的程度有关。提示异常表达ＨＬＡ－ＤＲ抗原在前列腺增生症的病理上有重要意义。     

Epidermal growth factor receptor mRNA levels in human prostatic tumors and cell lines.

The mitogenic activity of epidermal growth factor (EGF) is mediated by a cell surface receptor (EGF-R) which has been identified in human prostate tissues. Because of conflicting reports on the relative levels of EGF-R in prostate tumors as measured by binding of radiolabelled EGF, we have examined EGF-R expression at the level of the specific messenger RNA using a sensitive RNase protection assay. Expression of the mRNA for EGF-R was higher in carcinoma (CaP, N = 38) than in benign prostatic hyperplasia (BPH, N = 35) samples (p less than 0.01). The highest levels of EGF-R mRNA were found in the human prostatic carcinoma cell lines, PC-3 and DU145. Among the CaP samples, there was an association of higher EGF-R mRNA levels with higher tumor extent and dedifferentiation. Since EGF has also been found in prostatic tissues, the enhanced expression of the EGF-R gene may play a role in the growth of prostate tumors, possibly by an autocrine pathway.     

Epidermal growth factor receptor content in rat prostatic adenocarcinoma: effects of endocrine treatment

Epidermal growth factor receptor (EGF-R) was studied in Dunning prostatic cancer models using competitive bindings assays and solution hybridization assay. EGF-R-binding capacity and mRNA were demonstrated in a hormone-sensitive R3327 prostatic tumor from both control and castrated animals while no such activity was found in the hormone-independent AT-1 tumors. Castration induced no quantitative changes in the EGF-R. Estrogen treatment induced a significant reduction of the binding capacity of EGF-R and its mRNA. It was concluded that EGF-R is present in the androgen-sensitive Dunning prostatic tumor models (R3327), but that the androgen-insensitive, undifferentiated AT-1 tumor lacks EGF-R expression. Endocrine treatment has no significant effect on the EGF-R in these tumor models.     

Multiple responses to EGF receptor activation and their abrogation by a specific EGF receptor tyrosine kinase inhibitor

BACKGROUND: Epidermal growth factor receptor (EGF-R) autophosphorylation is essential for its intracellular mitogenic signaling via the MAPK pathway and for interaction in other cellular processes. Inhibition of this activity in tumor cells that predominantly utilise EGF-R therefore offers an alternative approach to therapy. METHODS: The ability of a specific inhibitor of EGF-R tyrosine kinase, ZM 252868, (TKI) to alter various parameters related to growth in DU145 and PC3 cell lines was investigated, by immunocytochemistry, Northern blotting, Western blotting and invasion assays. RESULTS: In DU145 cultures, the total cell population and number of cells in cell cycle decreased in the presence of TKI whilst the apoptotic rate was significantly increased. Reduction in autophosphorylation of the EGF-R, membrane expression of EGF-R, activation of the MAPK, p38, and JNK enzymes and the invasive capacity of DU145 cells was observed in the TKI treated cells. Under the same conditions, PC3 cell growth and EGF-R expression and MAPK activation were not affected. The use of inhibitors of intracellular signaling indicated that the DU145 cells, in contrast to PC3 cells, predominantly utilize EGF-R activation of the MAPK signaling pathway for growth. CONCLUSIONS: In prostatic cancer patients, in whom androgen resistance has developed and whose tumors have upregulated EGF-R for growth, specific TKI's may offer an important therapy option.     

Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer

BACKGROUND: Alpha-methylacyl-CoA racemase (AMACR) is strongly expressed in prostate cancer with variable expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and low expression in normal prostate. We examined whether AMACR expression in HGPIN and normal tissue was associated with subsequent diagnosis of cancer or proximity to a cancer focus. METHODS: Needle core biopsies from 45 patients with isolated HGPIN, 12 radical prostatectomy (RP) specimens with prostatic carcinoma and 6 cystoprostatectomies without prostatic carcinoma were immunostained for AMACR. Among patients with HGPIN, 23 (cases) showed cancer on a later biopsy and 22 (controls) had no cancer with at least 3 consecutive negative biopsies. RESULTS: In the biopsy set, the mean AMACR expression per gland in the normal compartment of the cases (0.29) was significantly higher than the controls (0.21) (P = 0.0006). In the RP set, normal glands near a cancer focus had higher mean AMACR expression than those that were distant (P = 0.0006). There was no difference within the HGPIN compartment between cases and controls in the biopsies, or between near and distant glands in the RP set. Mean AMACR staining of normal glands in the cystoprostatectomy specimens was significantly lower than in normal glands in close proximity to a cancer focus. CONCLUSIONS: Higher expression of AMACR in normal glands near a focus of cancer, as well as in the subjects eventually showing cancer, suggests a possible field effect in prostatic carcinogenesis. AMACR expression in normal glands therefore might be a useful predictor for repeat biopsy outcomes or as an intermediate endpoint in chemoprevention studies.     

Amphiregulin expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 93 cases

BACKGROUND: Amphiregulin (AMP) is a heparin-binding glycoprotein that is structurally and functionally related to epidermal growth factor. Its effects are mediated by the tyrosine kinase activity of the epidermal growth factor receptor (EGF-R), and specific nuclear targeting sequences. AMP induces cell proliferation after androgen stimulation of human prostate cancer cell lines. An autocrine proliferative loop involving AMP, androgen, and EGF-R may, therefore, play a role in prostatic carcinogenesis. The purpose of this study was to compare the expression of AMP in benign prostatic epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. METHODS: We performed an immunohistochemical study of select sections from 93 radical prostatectomies performed at the Mayo Clinic between 1987 and 1991. All patients were previously untreated and found to have pathologic stage T2N0M0 adenocarcinoma after routine handling of surgical specimens. Affinity-purified polyclonal antibody directed against AMP was applied to tissue sections using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in 10% increments. Intensity on a scale from 0 (negative) to 3 (strongly immunoreactive) and pattern of expression (nuclear versus cytoplasmic) also were recorded. RESULTS: AMP immunoreactivity was present in benign prostatic epithelium, PIN, and prostatic adenocarcinoma in all cases. The mean percentage of AMP-immunoreactive cells was 53.8% in benign epithelium, 65.9% in PIN, and 74.3% in cancer. Intensity was moderate in all cases. The pattern of expression was usually nuclear in benign epithelium (secretory and basal cells), and usually cytoplasmic or nuclear and cytoplasmic in PIN and adenocarcinoma. There were rare scattered immunoreactive cells in the stroma, ejaculatory duct epithelium, and urethral urothelium. Endothelial cells were invariably unstained. CONCLUSIONS: AMP expression in prostate increases progressively from benign epithelium to PIN and cancer. Increased expression of AMP may contribute to the development of prostatic adenocarcinoma. Predominantly nuclear staining was observed in benign epithelium, whereas cytoplasmic or nuclear and cytoplasmic staining was observed in PIN and adenocarcinoma. The differences in nuclear and cytoplasmic localization of immunoreactivity may reflect the presence of two pathways of activation, and hence varying biological functions of AMP.     

CD147在前列腺癌组织中阳性表达与PSA失败的相关性分析

目的探讨CD147在前列腺癌组织中的表达情况及其临床意义。方法应用免疫组化S—P法检测240例前列腺癌组织中CD147的表达情况,并对CD147与前列腺癌PSA失败的关系进行统计学分析。结果CD147在无PSA失败前列腺癌组织中的阳性率为27．6％．有PSA失败的阳性率为80．7％,具有显著差异（P〈0．05）。CD147的表达与PSA失败呈正相关。结论CD147检测有助于了解前列腺癌的恶性程度,评估其预后,对临床制定治疗方案有指导意义。     

Differential expression of TRAIL and its receptors in benign and malignant prostate tissues

PURPOSE: Because TRAIL (tumor necrosis factor related apoptosis inducing ligand) selectively kills cancer cells without damaging normal cells, a gene therapy approach using TRAIL is feasible for treating patients with cancer. However, recent publications suggest that significant portions of human tumors appear to be TRAIL resistant. Furthermore, there is some controversy about whether TRAIL receptor composition influences TRAIL sensitivity in cancer cells. Our recent studies suggest that TRAIL receptor composition is the major modulator of TRAIL sensitivity, as demonstrated using prostate, breast and lung cancer cells. We investigated TRAIL and TRAIL receptor expression profiles during prostate carcinogenesis to evaluate their potential as biomarkers and predict the feasibility of a related gene therapy approach. MATERIALS AND METHODS: Paraffin embedded prostate tissues of 44 patients with benign prostatic hyperplasia, 28 with organ confined prostate carcinoma and 26 with advanced prostate carcinoma were analyzed using immunohistochemical staining procedures. RESULTS: Significant levels of TRAIL-R4 decoy receptor expression were detected in patients with benign prostatic hyperplasia, and organ confined and advanced prostate carcinoma. All TRAIL markers tested appear to be valuable markers for separating patients with benign prostatic hyperplasia from patients with organ confined prostate carcinoma or advanced prostate carcinoma. CONCLUSIONS: Due to high TRAIL-R4 expression in all patient groups complementary gene therapy modalities might be needed to bypass potential TRAIL-R4 induced resistance.     

良、恶性前列腺病变组织P53、C-erbB-2和EGF-R表达及其临床意义

目的 探讨P_(53)、C-erbB-2和EGF-R在良、恶性前列腺病变组织中的表达差异及其临床意义。方法 采用免疫组织化学ABC法,分别对34例良性前列腺增生(BPH)、29例前列腺癌(Pca)组织中P_(53)、C-erbB-2和EGF-R表达进行研究。结果 在29例Pca中P~(53)阳性染色5例,阳性率为17％(5/29),而在良性前列腺组织中则无一例阳性染色(P<0.05)。在良性前列腺增生征中C-erbB-2和EGF-R阳性表达率分别为18％(6/34)和88％(30/34);而在前列腺癌中C-crbB-2和EGF-R的阳性率分别为21％(6/29)和17％(5/29),前列腺癌分期和分级与P_(53)、C-erbB-2和EGF-R的表达之间没有明显的相关性(P>O.05)。结论 尽管P_(53)、EGF-R在良性,恶性前列腺病变之间表达有差异(P<0.05),但是他们与肿瘤的分期和分级等预后因素无关。     

直肠癌旁移行黏膜的分布规律及survivin基因表达的意义

目的　探讨survivin基因在直肠癌旁移行黏膜中的表达及意义。方法　应用黏液组化方法检测了解各种组织类型直肠癌旁移行黏膜的分布规律 ,应用免疫组化方法检测凋亡抑制基因sur vivin在直肠癌及癌前状态的表达情况。结果　黏液癌的癌旁移行黏膜范围平均为 7.83cm ,明显大于乳头状癌及管状腺癌 (P <0 .0 1) ;癌旁移行黏膜DukesC期平均 5 .61cm ,明显大于DukesA ,B期 (P<0 .0 5 ) ;正常黏膜 (NM )、移行黏膜 (TM )、非典型增生黏膜及癌组织中均有survivin基因产物表达 ,由正常直肠黏膜到癌组织表达率逐渐增加 ,4组间差别均有显著意义 (P <0 .0 5 )。结论　在非典型增生及癌组织存在survivin基因表达上调 ,提示survivin基因对直肠癌的发生发展起重要作用 ,有望成为直肠癌基因治疗的新靶点。在黏液癌及DukesC期直肠癌旁移行黏膜范围明显增宽 ,提示对低位黏液癌及DukesC期直肠癌保肛手术应持慎重态度。