不同前列腺组织中雄激素受体的表达研究

目的:研究雄激素受体(AR)在正常前列腺、良性前列腺增生(BPH)和前列腺癌(PCa)组织中的表达,探讨AR与BPH和PCa的关系。方法:采用实时定量PCR、免疫荧光和组织蛋白电泳方法,分析15例正常前列腺、20例BPH与40例PCa标本中AR的表达情况。结果:实时定量PCR和组织蛋白电泳检测BPH组织与正常前列腺组织中AR的表达量差异无统计学意义(P>0.05)。但免疫荧光检测发现BPH组织中AR蛋白表达量增高。3种方法检测PCa组织中AR表达量较正常前列腺组织和BPH组织增高(P<0.05)。高分化PCa的AR表达比低分化PCa高(P<0.05)。随着临床分期的增高,AR的表达降低(P<0.05),激素非依赖性前列腺癌(HRPC)组织中AR表达最低。结论:AR在PCa组织中的表达较正常前列腺和BPH组织中增高,AR的表达与PCa的分级、分期相关。     

Caspase-1在良性前列腺增生组织中的表达及意义

目的:探讨正常和良性前列腺增生(BPH)组织中的caspase-1表达情况及意义。方法:应用免疫组化SP法分别检测21例BPH组织和7例正常前列腺组织标本中caspase-1的表达。结果:caspase-1阳性表达率在BPH组织中为71.4%(15/21),正常前列腺组织中为100%(7/7)。BPH上皮组织和间质组织的caspase-1阳性表达均比正常前列腺明显减少(P<0.01)。在BPH组织内部,上皮的caspase-1阳性表达明显高于间质(P<0.01)。结论:caspase-1在BPH组织中的表达较正常前列腺组织显著减少,提示由caspase-1介导的凋亡过程的减少可能参与了BPH的发病过程。     

组织激肽释放酶基因7在前列腺癌组织中的表达

目的 探讨组织激肽释放酶基因7(KLK7)在不同前列腺组织中的表达情况.方法运用逆转录聚合酶链反应法检测正常前列腺(5例)、良性前列腺增生(BPH)及BPH细胞株(BPH1,13例)、前列腺癌及前列腺癌细胞株(8例)的上皮细胞中KLK7mRNA表达水平;蛋白质印迹法检测不同前列腺组织上皮细胞中KLK7蛋白表达水平;免疫组化分析正常前列腺(20例)、BPH(50例)、前列腺癌(103例)组织中KLK表达水平.根据染色强度分为4个等级(-,+,++,+++)进行半定量分析,染色强度++及+++者判定为阳性.结果 正常组、BPH组和前列腺癌组KLK7 mRNA表达相对值分别为0.59、0.52、0.02,组间比较差异有统计学意义(F=13.03,P＜0.01),前列腺癌上皮中KLK7 mRNA表达下调(P＜0.01),正常前列腺和BPH上皮中KLK7 mRNA表达差异无统计学意义(P＞0.05).KLK7蛋白在正常前列腺、增生前列腺、DU145、LNCaP、PC3、22RV1、BPH细胞株中表达水平相对值分别为0.22、0.40、0.01、0.05、0、0.03、0.14.免疫组化染色结果 显示正常前列腺组织、BPH组织、前列腺癌中KLK7蛋白表达阳性率分别为65.0%(13/20)、76.0%(38/50)、17.5%(18/103),前列腺癌组与前2组比较差异均有统计学意义(P＜0.01),前2组间比较差异无统计学意义(P＞0.05).结论 KLK7在前列腺癌组织中表达下调,提示KLK7在前列癌的发生和进展中可能起一定作用.     

α-甲基-辅酶A消旋酶在前列腺癌中的表达及意义

目的　探讨α 甲基 辅酶A消旋酶 (P5 0 4S)表达在国人前列腺癌病理诊断中的价值。　方法　对 4 2例前列腺癌、18例前列腺上皮内瘤 (PIN)和 2 5例良性前列腺增生 (BPH)标本进行P5 0 4S、高分子质量角蛋白 (34βE12 )和血管内皮生长因子 (VEGF)免疫组化染色 ,观察比较分析染色范围和强度。　结果　前列腺癌标本P5 0 4S染色阳性 33例 (79% ) ,染色强度为中等到强阳 ,明显高于BPH和PIN ,癌旁组织均为阴性 ;6例 (33% )PIN标本 ,2例 (8% )BPH标本有少量细胞微弱表达 ,其余均为阴性。BPH标本具有完整基底层细胞 ,34βE12 呈阳性表达 ;PIN腺体基底层细胞 34βE12 表达阳性 ,相对BPH强度减弱 ;4 0例前列腺癌腺体无基底层细胞 ,仅 2例有不完整的基底层呈弱表达。BPH、PIN和前列腺癌标本VEGF均呈阳性表达 ,各组阳性细胞数和染色强度相差不明显。　结论　P5 0 4S诊断前列腺癌敏感性高、特异性好 ,结合 34βE12 检测可提高前列腺癌的检出率。     

α-甲酰辅酶A消旋酶免疫组化染色--诊断前列腺癌的新方法

目的探讨α-甲酰辅酶A消旋酶(AMACR,P504s)免疫组化染色在前列腺癌诊断中的价值.方法前列腺癌(PCa)标本46例(A期1例,B期19例,C期14例,D期12例;Ⅰ级4例,Ⅱ级14例,Ⅲ级28例),良性前列腺增生(BPH)53例,前列腺上皮内瘤(PIN)13例,正常前列腺9例,前列腺炎6例,膀胱癌转移前列腺3例,前列腺间质肉瘤、鳞癌、未分化癌各1例.平均年龄71岁.采用HE染色及P504s的兔单克隆抗体行免疫组化分析.P504s表达分为阴性(1分)、弱阳性(2分)、阳性(3分)、强阳性(4分).结果46例PCa标本中P504s阴性2例、弱阳性1例、阳性25例、强阳性18例,平均染色浓度3.28分(95%可信区间CI 3.07～3.50分);53例BPH标本中P504s阴性47例、弱阳性6例,平均染色浓度1.11分(95%CI 1.02～1.20分);13例PIN标本中P504s阴性12例、弱阳性1例,平均染色浓度1.08分(95%CI 0.91～1.24分).PCa组与BPH、PIN组差异有统计学意义(P＜0.001).正常前列腺、前列腺炎、前列腺间质肉瘤、鳞癌、未分化癌、膀胱癌转移前列腺标本P504s染色均为阴性.结论P504s检测诊断PCa有重要的参考价值.     

Caspase-3在前列腺组织中的表达和意义

目的 研究Caspase-3在良性前列腺增生(BPH)和前列腺癌(Pca)组织中的表达,了解Caspase-3在BPH和Pca发病及细胞凋亡中的作用。方法 30例BPH组织、22例Pca组织及7例正常前列腺石蜡切片组织用多克隆抗体Caspase-3行LSAB免疫组化染色,按表达的阳性率分0(阴性)、1 (<25％)、2 (25％～75％)、4 (>75％)统计染色等级。结果Caspase-3在93％(28/30)BPH组织有不同程度的表达(0～3 ),主要在分泌性上皮和基底细胞表达,而在基质平滑肌罕见表达,且BPH上皮表达明显少于正常组织。Capase-3在22例Pca组织表达阳性率为100％,普遍表达强阳性(4 ),且明显多于非癌性组织,Caspase-3表达与Pca病理分级无相关。结论 Caspase-3表达异常与BPH上皮与基质增生有关;Caspase-3在国人Pca细胞凋亡中有重要作用。     

SAM68和SENP-1在前列腺癌组织中的表达及临床意义

探讨SAM68与SENP-1在前列腺癌组织中的表达及其临床意义。方法 收集2014年1月至2018年1月在本院未经相关治疗初次行穿刺活检或手术切除的前列腺组织标本94例，免疫组化法检测50例前列腺癌组织和44例良性前列腺增生组织中SAM68与SENP-1的表达情况，并结合临床病理学资料进行统计分析。结果 免疫组化结果显示：SAM68与SENP-1在前列腺癌组织中的阳性表达率明显高于前列腺增生组织(P<0.001)。SENP-1与SAM68的表达均与分化程度、TNM分期及骨转移相关(P<0.05)；相关性分析显示：SENP-1与SAM68表达呈正相关（r=0.463，P<0.001）。结论 SAM68与SENP-1在前列腺癌组织中高表达，并与前列腺癌的发生和恶性进展有关，且有望成为前列腺癌诊断和治疗的潜在靶点。     

前列腺癌组织中前列腺跨膜上皮抗原表达的临床意义

目的 :探讨前列腺跨膜上皮抗原 (STEAP)在前列腺癌 (PCa)组织中的表达及与肿瘤病理分级之间的关系。方法 :采用免疫组化SP法 ,用STEAP单克隆抗体对前列腺不同病变组织及非前列腺肿瘤组织石蜡包埋切片进行免疫组化染色 ,其中PCa组织 131例 ,良性前列腺增生 (BPH)组织 16 4例 ,非前列腺肿瘤组织标本 5 6例。引入阳性面积单位概念判定STEAP染色强度。　结果 :2 95例前列腺病变组织中 ,仅 3例PCa和 5例BPH组织STEAP呈阴性表达 ,STEAP在PCa组织中明显高表达 ,非前列腺肿瘤组织染色均呈阴性。STEAP表达与PCa的Gleason分级之间存在显著负相关性。　结论 :STEAP能够用来判断PCa的预后 ,在PCa的免疫治疗方面具有良好的应用前景。     

前列腺组织EGFR和PCNA表达的相关性

目的 探讨前列腺良、恶性组织中EGFR、PCNA的表达及其相关性。方法 应用免疫组织化学ABC法检测36例前列腺癌(PCa),20例前列腺增生(BPH)组织中EGFR、PCNA的表达情况。结果 BPH组EGFR阳性表达率高于PCa组(45％vs17%,P<0.25);PCa组比BPH组细胞增生活跃(P<0.01)。EGFR阳性表达的前列腺癌比EGFR阴性者细胞增殖活跃(P<0.05)。PCNA阳性表达随肿瘤分级增高而增高(P<0.05)。结论 EGFR可能参与BPH的增生过程,而PCNA则是判断前列腺癌细胞增殖状态、恶性度的指标,在前列腺癌的发生中起一定作用。     

前列腺增生与前列腺癌特异性膜抗原mRNA的表达

目的以实时荧光定量聚合酶链反应(PCR)技术研究良性前列腺增生(BPH)与前列腺癌(Pca)组织标本PSMmRNA的表达,探讨前列腺特异性膜抗原(PSM)在前列腺癌诊断的特异性意义。方法通过实时荧光定量PCR对23例PCa、37例BPH及3例正常前列腺组织PSMmRNA的表达,比较其在3种组织定量的差异。结果BPH与PCa组织PSMmRNA的定量表达值分别为1.54±0.21与4.95±0.78,差异有统计学意义(P<0.05)。结论实时荧光RTPCR定量检测PSMmRNA为前列腺癌的诊断、治疗、预后监测等提供了更为可靠的辅助指标。     

PSA"灰区"值时前列腺癌组织中Trp-p8的表达及意义

目的 研究Trp-p8蛋白在PSA"灰区"前列腺组织中的表达规律,探讨其在前列腺癌(PCa)早期诊断中的作用.方法 通过免疫组织化学的方法研究了28例PSA"灰区"前列腺组织中Trp-p8蛋白的表达情况,其中前列腺增生症(BPH)和PCa标本各14例,采用图文数据成像分析系统判定各组织中Trp-p8蛋白的表达强度,分析其差异性.结果 BPH中Trp-p8蛋白的表达强度较弱,呈不表达或微量表达.在PCa组织中Trp-p8蛋白均呈不同程度的阳性表达,这种表达差异具有统计学意义.结论 Trp-p8在PSA"灰区"前列腺组织中的表达存在差异,在PCa组织中Trp-p8蛋白的表达强度高于BPH组织,这种差异性表达对于早期PCa诊断具有重要意义.     

BPH相关性抗原表达的临床意义

目的:探讨BPH相关性抗原(BPSA)在BPH、前列腺癌(PCa)诊断中的作用。方法:采用免疫组织化学ABC法,用BPSA单克隆抗体对62例BPH患者、37例PCa患者及30例其他肿瘤组织标本中的BPSA表达进行检测。结果:BPSA在100% BPH、88% PCa组织中呈不同程度的阳性表达,且在BPH组织中呈明显高表达。非前列腺肿瘤组织染色均呈阴性。组织BPSA表达与肿瘤病理分级无相关性(P>0. 05)。结论:BPSA具有良好的组织器官特异性,有助于早期PCa和BPH的鉴别诊断。     

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.     

前列腺癌组织中HMGA2的表达及其意义

目的探讨高迁移率族蛋白HMGA2在前列腺癌中的表达及其意义。方法采用免疫组化法及RT—PCR法检测40例前列腺癌组织及良性前列腺增生组织中HMGA2的表达情况。结果RT-PCR法检测示良性前列腺增生组织中HMGA2少量表达;恶性组织中,随着病理分级增加,HMGA2mRNA相对表达量逐渐增高,免疫组化法显示前列腺癌组织中,有75．0％（30／40）HMGA2呈阳性表达。良性前列腺增生组织与前列腺癌组织两组间差异显著（t=3．32,P〈0．001）。结论HMGA2在前列腺癌中呈过度表达,并与前列腺癌病理分级有关,可能成为前列腺癌诊断与良恶性鉴别诊断的指标之一。     

MUC1 Expression in Prostate Carcinoma: Correlation with Grade and Stage

Mucins have been implicated in the biologic behavior and progression of several types of cancer. The aims of this study were to define the expression pattern of one particular mucin, MUC1, in benign and malignant human prostate tissue and to determine if MUC1 expression correlates with tumor grade and stage. Immunohistochemical staining utilizing an anti-MUC1 monoclonal antibody was performed on 4 fetal prostates, 4 specimens of benign prostatic hyperplasia (BPH), and 34 radical prostatectomy specimens. In human fetal and BPH specimens, there was an apical pattern of MUC1 expression, similar to that reported in other normal and benign tissues. Ninety-four percent of the prostate cancers were MUC1 positive. A high percentage of prostate cancer specimens (62%) demonstrated a diffuse, cytoplasmic staining pattern. There was a statistically significant correlation between diffuse MUC1 staining and Gleason pattern, with a diffuse/total staining percentage of 9% in Gleason 2, 64% in Gleason 3, 80% in Gleason 4, and 100% in Gleason 5. More diffuse staining was also seen in samples from patients with high pathologic stage: 21% in T(2), 75% in T(3), and 67% in N(1) disease. These data indicate that MUC1 expression is prevalent in prostate cancer and that diffuse cytoplasmic staining correlates with advanced Gleason pattern and advanced pathologic stage.     

Immunohistochemical finding of α-1-antichymotrypsin in tissues of benign prostatic hyperplasia and prostate cancer

BACKGROUND: Ratio of free to total (F/T) prostate-specific antigen (PSA) is higher in the blood of patients with benign prostatic hyperplasia than those with prostate cancer. To clarify the difference between ratios in these two, alpha-1-antichymotrypsin, the major component of the bound PSA in the blood, was immunohistochemically examined. METHODS: Tissues were obtained surgically via a retropubic approach from patients with benign prostatic hyperplasia (nine cases) and prostate cancer (27 cases). These samples were processed in paraffin blocks, cut into 5 mm sections and stained with antibodies against alpha-1-antichymotrypsin and PSA. RESULTS: The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer was higher than that in benign prostatic hyperplasia (P<0.05). Almost all of glandular and cancer cells were stained with PSA antibody. The percentage of alpha-1-antichymotrypsin-stained cells in prostate cancer did not correlate to histologic grade, although alpha-1-antichymotrypsin-stained cells were more widely scattered in high grade tissues. No correlation was found between alpha-1-antichymotrypsin-stained cells and ratio of F/T in the blood of cancer patients. In about 20% of cancer tissues, histiocytes with positive alpha-1-antichymotrypsin staining were found in stroma but not in that of benign prostatic hyperplasia. CONCLUSIONS: Prostate cancer tissues are shown to have a richer environment of alpha-1-antichymotrypsin than those of benign prostatic hyperplasia. Some cancer tissues contained alpha-1-antichymotrypsin-stained histiocytes. These local events may correlate to a high amount of the bound form among total PSA in the blood of prostate cancer patients.     

The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer

OBJECTIVE: To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS: The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS: Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS: TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.     

P504S immunohistochemical detection in 405 prostatic specimens including 376 18-gauge needle biopsies

P504S is a recently described, prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. A recent study has shown that immunohistochemical detection of P504S gene product is a sensitive and specific marker of prostatic carcinoma in formalin-fixed, paraffin-embedded tissues. We performed a detailed analysis of P504S protein expression in a large series of prostate and bladder specimens with special emphasis on staining in specific morphologic patterns of prostatic adenocarcinoma, posthormonal and radiation therapy cases, and invasive urothelial carcinoma. A total of 366 prostate needle core biopsies from 124 patients with prostate cancer, 10 biopsies from 2 patients without prostate cancer, 28 prostatectomy specimens (16 with specific morphologic patterns, 7 posthormonal therapy and 5 postradiation therapy specimens), 5 bladder specimens with invasive urothelial carcinoma, and a single transurethral resection specimen from a patient with hormonally treated prostate cancer and invasive urothelial carcinoma were stained with P504S monoclonal antibody at a 1:250 dilution using standard heat-induced epitope retrieval and avidin-biotin technique. Extent (0, no staining; 1+, 1-10% staining; 2+, 11-50% staining; 3+, > or =51% staining) and location (luminal, subluminal, and diffuse cytoplasmic) of immunoreactivity in carcinoma and benign tissues were recorded. A total of 153 of 186 biopsies (82%) with prostatic adenocarcinoma stained for P504S. Pseudohyperplastic, atrophic, ductal, and mucinous prostatic carcinomas stained similarly, as did cases treated with hormone or radiotherapy. In 81 of 377 (21%) foci of benign prostatic tissue there was staining that was almost always focal, faint, and noncircumferential. Seminal vesicles did not stain for P504S. Five of six (83%) specimens with invasive urothelial carcinoma had 2+ staining and one case had focal staining. We conclude that immunohistochemistry for P504S has potential utility in the diagnosis of prostate cancer, including those treated by hormones and radiation. Circumferential luminal to subluminal and diffuse cytoplasmic staining is the most specific staining pattern for prostatic carcinoma and is almost never associated with benign prostatic tissue. However, a negative P504S immunostain does not automatically rule out prostate cancer, as 18% of cases were negative. Additionally, occasional benign glands, high-grade prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, and urothelial carcinoma may express P504S. Therefore, we think that P504S is best used only in conjunction with strict light microscopic correlation and preferably with high molecular weight cytokeratin immunostaining.     

Immunohistochemical expression of tumor antigens MAGE-A1, MAGE-A3/4, and NY-ESO-1 in cancerous and benign prostatic tissue

OBJECTIVE: To investigate immunohistochemical expression of MAGE-A and NY-ESO-1/LAGE-1, cancer testis antigens in prostate tissues showing evidence of malignant transformation or benign hyperplasia. METHODS: 112 prostate samples from patients undergoing surgery at the Urology Clinic at the Zagreb Clinical Hospital Center from 1995 to 2003 were investigated in this study. Of these, 92 carcinoma samples were obtained by radical prostatectomy, and 20 benign prostatic hyperplasia samples by transvesical prostatectomy. Three monoclonal antibodies were used for immunohistochemical staining: 77B for MAGE-A1, 57B for multi-MAGE-A and D8.38 for NY-ESO-1 expression. RESULTS: Expression of MAGE-A1 was observed in 10.8% of carcinoma samples, whereas multi-MAGE-A and NY-ESO-1/LAGE-1 stained 85.9% and 84.8% of samples. Immunohistochemical staining was only detectable in the cytoplasm. A significant heterogeneity could be observed within a same tissue sample where areas with strong positivities coexisted with cancer testis antigens negative areas. Interestingly, a majority of 57B positive cases were also found to be D8.38 positive (correlation coefficient r=0.727 (P<0.01)). Cancer testis antigens expression was neither significantly correlated with PSA values nor with Gleason score. In benign prostatic hyperplasia tissues MAGE-A1 expression was detected in 5%, while 57B and D8.38 staining was observed in 15% samples, and in all cases percentages of positive cells were always <10%. CONCLUSION: Our data underline the peculiar relevance of cancer testis antigens expression in prostate cancers, with potential implications regarding both diagnosis and therapy.     

Caspase 3 expression in benign prostatic hyperplasia and prostate carcinoma

BACKGROUND: Apoptotic resistance to androgen ablation represents a significant problem in the treatment of prostate cancer. Over expression of antiapoptotic proteins such as Bcl-2 and mutations in p53 contribute to this resistance. The caspase family of proteases are central executioners of the cell death pathway. They are expressed in normal prostate secretory epithelial cells. Altered expression may represent an additional component leading to cell resistance. The aim of this study was to determine by immunohistochemistry caspase 3 expression in benign prostatic hyperplasia and prostate cancers. METHODS: Twenty-two patients with histologically determined prostate cancer and benign prostatic hyperplasia (BPH) were investigated. All specimens were obtained from patients undergoing surgical resection of the prostate. Immunohistochemical analysis was performed on formalin fixed paraffin embedded sections to assess caspase 3 expression. RESULTS: Caspase 3 was expressed in 18/22 (81.1%) samples, with high expression in BPH which demonstrated staining in both basal and secretory epithelial cells. Increasing grades of prostatic cancer showed a significant loss of expression in secretory epithelial layers and little staining in epithelial cells in high-grade prostatic carcinoma. CONCLUSIONS: Altered caspase 3 expression may represent an additional mechanism of apoptotic resistance to androgen ablation. Prostate 47:183-188, 2001.