丝裂素活化蛋白激酶p38在前列腺上皮内瘤的表达及其意义

目的：探讨丝裂素活化蛋白激酶p38（p38MAPK,p38）在前列腺肿瘤形成过程中的作用。方法：采用免疫组织化学SP法检测12例前列腺上皮内瘤（PIN）和12例前列腺增生（BPH）组织中p38的表达。结果：p38在PIN中主要分布于腺上皮和肿瘤细胞,呈片状、弥漫状分布。在BPH中主要分布于腺上皮基底细胞,分泌细胞有少量着色。PIN和BPH组织中p38的活性表达分别为（63．83±18．34）％和（48．75±16．94）％,两组间比较,差异有统计学意义（P〈0．05）。结论：PIN组织中p38的活性显著高于BPH。p38活性的增强参与了前列腺上皮的恶性转化,可能在前列腺肿瘤的发生、发展中起着重要作用。     

细胞增殖核抗原在前列腺上皮内瘤中的表达

目的:研究细胞增殖核抗原(PCNA)在前列腺上皮内瘤(PIN)组织中的表达,探讨细胞增殖在前列腺肿瘤形成过程中的作用.方法:采用免疫组织化学方法检测12例PIN和12例良性前列腺增生(BPH)组织中PCNA的表达.结果:PIN组织中PCNA阳性细胞主要分布于腺上皮的基底细胞层与分泌细胞层,在BPH组织中主要见于腺上皮基底细胞层.PIN和BPH组织中细胞增殖指数分别为(15.92±4.40)%和(8.33±2.93)%,两组间比较差异有统计学意义(P＜0.01).结论:PIN组织中细胞增殖活性显著高于BPH,增强的细胞增殖活性参与了前列腺上皮的恶性转化,在前列腺肿瘤的发生、发展中起重要作用.     

细胞外信号调节蛋白激酶在前列腺上皮内瘤组织中的表达及意义

目的 探讨细胞外信号调节蛋白激酶（ERK）在前列腺上皮内瘤（PIN）组织中表达的意义。方法 应用免疫组织化学SP法检测12例PIN、11例前列腺癌（PCa)及16例BPH组织标本中ERK的表达。结果 12例PIN标本均有表达,其中6例为高表达;11例PCa组织10例为阳性,但多为弱表达;16例BPH组织12例为阳性,表达也较弱。PIN组织中ERK表达与PCa组和BPH相比ERK在PIN组织中呈高表达,与早期前列腺癌的发生有密切关系。     

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。     

前列腺特异性膜抗原和前列腺特异性抗原在前列腺癌组织中的表达

目的：观察并比较前列腺特异性膜抗原（PSMA）和前列腺特异性抗原（PSA）在不同前列腺为组织中的表达差异；比较组织PSMA与PSA对前列腺癌诊断和鉴别诊断的意义。方法：采用ABC三步法免疫组织化学染色方法，用PSMA和PSA单克隆抗体对70例前列腺癌（PCA）、21例前列腺上皮内瘤（PIN）、20例前列腺良性增生（BPH）组织进行染色。结果：PSMA在前列腺癌组织中明显高表达，PSA则在前列腺良性增生组织中高表达；组织PSMA对前列腺癌的阳性检出率明显高于PSA。结论：PSMA是较PSA更具特异性的前列腺癌瘤标，可望取代PSA成为诊断前列腺癌的新型瘤标，并在前列腺癌免疫治疗方面具有良好的应用前景。     

P504S、CK34βE12、p63、PSA在前列腺腺癌病理诊断中的应用

目的探讨P504S（α-甲酰基-辅酶A消旋酶）、高分子细胞角蛋白（CK34βE12）、p63、前列腺特异性抗原（PSA）在前列腺腺癌病理诊断中的应用价值。方法对46例前列腺腺癌、8例前列腺高级别上皮内瘤（HGPIN）和35例良性前列腺增生（BPH）标本进行P504S、CK34βE12、PSA、p63和免疫组织化学染色。结果46例前列腺腺癌标本中，P504S阳性表达42例（91＋3％），其中弥漫性胞质阳性（＋＋＋）25例（54＋3％），HGPIN标本阳性7例（87．5％），1例（2．9％）BPH标本有少量腺体微弱表达；HGPIN标本中CK34βE12及p63连续或断续表达8例（100．0％），BPH标本阳性表达33例（94．3％），46例前列腺腺癌标本均未见表达；前列腺腺癌标本中PSA阳性表达44例（95．7％）。结论P504S诊断前列腺腺癌敏感性高，特异性较好，结合HE切片、CK34βE12、p63和PSA等免疫组织化学染色检测可提高前列腺腺癌病理诊断的准确性。     

p27^kip1在前列腺上皮内瘤细胞中的表达

目的：研究前列腺上此内瘤（PIN）细胞中p27kipl的表达。方法：采用免疫组织化学分析法。检测22例人前列腺标本中PIN细胞p27kip1蛋白的表达。结果：在22例人前列腺标本中,高分级PIN灶细胞中p27kipo1蛋白表达与周边前列腺上此细胞比较均有降低。结论,p27kip1蛋白表达降低可能和PIN的形成有关。     

BPH和前列腺腺癌中Livin的表达及其意义

目的：探讨凋亡抑制因子Livin在BPH和前列腺腺癌中的表达及其临床意义。方法：采用免疫组织化学SP法,用Livin单克隆抗体对10例BPH、30例前列腺腺癌和10例正常前列腺组织中Livin基因的表达进行检测,分析其在正常前列腺组织、BPH组织和前列腺腺癌组织中的表达状况,以及Livin基因的表达与前列腺腺癌病理学分级之间的关系。结果：Livin基因在10例正常前列腺组织中均不表达,而在10例BPH组织中有8例呈阳性表达（80％）,在30例前列腺腺癌中有21例呈阳性表达（70％）。Livin基因在正常组织中的阳性表达率与在BPH、前列腺腺癌中的阳性表达率差异有明显的统计学意义（P〈0．01）;Livin基因在BPH和前列腺腺癌中的阳性表达率差异无明显的统计学意义（P〉O．05）;Livin基因的表达和前列腺腺癌的分级无明显关系（P〉0．05）。结论：细胞凋亡抑制因子Livin在BPH和前列腺腺癌组织中的表达上调,提示Livin基因可能通过抑制细胞凋亡对BPH和前列腺腺癌的发生和发展起重要作用。检测Livin基因的表达对鉴定前列腺组织的良恶性方面无明显作用。     

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。     

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.     

Bcl-2 proto-oncogene expression in low- and high-grade prostatic intraepithelial neoplasia

OBJECTIVE: To determine the incidence of bcl-2 protein expression in low- and high-grade prostatic intra-epithelial neoplasia (PIN) lesions, and to explore the role of bcl-2 in prostatic tumorigenesis. Materials and methods Immunoreactivity for bcl-2 was examined in 10 samples of benign prostatic hyperplasia (BPH), 13 of primary prostatic adenocarcinoma, 15 of high-grade PIN and 18 of low-grade PIN. All immunostaining results were scored for the approximate percentage of positive tumour cells and relative immunostaining intensity (score range 0-12). RESULTS: In all BPH samples, bcl-2 staining was detected consistently in the basal cell layer of the ducts and acini, but no staining was ever apparent in luminal cells. The immunoreactivity for bcl-2 was heterogeneous in the prostatic carcinomas and bcl-2 protein expression was present in six samples. In these six bcl-2-positive tumours, the mean (range) staining score was 1.15 (1-6). There was detectable expression of bcl-2 in low- and high-grade PIN in all cell layers; immunoreactivity was present in 10 of 15 high-grade PIN lesions, with a mean (range) score of 1.14 (1-4), and in 12 of 18 samples of low-grade PIN, with a mean (range) score of 1.77 (1-6). CONCLUSIONS: The high incidence of bcl-2 protein expression in low- and high-grade PIN lesions suggests that bcl-2 protein expression is associated with early prostate tumorigenesis.     

Upregulation of erythropoietin receptor in human prostate carcinoma and high-grade prostatic intraepithelial neoplasia

The aim of the present study was to investigate the differential expression of erythropoietin receptor (EPOR) in prostate carcinoma (PCa), high-grade prostatic intraepithelial neoplasia (PIN), prostatic hyperplasia (BPH) lesions and normal prostatic tissues by immunohistochemistry; and to test the hypothesis that upregulation of EPOR is a specific event for prostate carcinogenesis. An immunohistochemical analysis of EPOR was performed on 30 PCa, 50 BPH with/without inflammation lesions and 30 normal prostatic tissue samples. EPOR staining was quantitated and classified into normal expression and overexpression. Totally 16 high-grade PIN lesions were found in this study. Overexpression of EPOR was shown only in PCa and high-grade PIN. Statistical analysis demonstrated that higher median EPOR staining score of PCa and high-grade PIN in comparison with BPH (P < 0.05) and higher median EPOR staining score of PCa compared with high-grade PIN (P < 0.05). Our data demonstrate that upregulation of EPOR is not uncommon for PCa and upregulated EPOR in high-grade PIN suggests upregulation of EPOR is an early event for prostate carcinogenesis. The role of upregulated EPOR and possibly enhanced EPOR signaling in prostate carcinogenesis warrants further studying.     

Immunohistochemical analysis with anti-cytokeratin antibody in the prostatic epithelium

PURPOSE: We performed immunohistochemical studies of the prostatic epithelium using three different anti-cytokeratin monoclonal antibodies (35 beta-H11, RCK108, and 34 beta-E12), and also investigated the immunoreactivity of various prostatic lesions with basal cell specific anti-cytokeratin antibody (34 beta-E12). MATERIALS AND METHODS: One hundred and thirty one prostatic specimens were obtained at surgery or biopsy. H-E stained sections were available for review in all cases. They were classified according to histopathology; benign prostatic hyperplasia (BPH), prostatic cancer (PCA), atrophic acini, atypical adenomatous hyperplasia (AAH), and prostatic intraepithelial neoplasia (PIN). ABC or LSAB method was utilized for immunohistochemical staining with 3 anti-cytokeratin monoclonal antibodies. RESULTS: 35 beta-H11 was mainly stained in the luminal cells and RCK108 was stained both in the luminal and the basal cells in BPH. 35 beta-H11 showed highly positive staining in the prostatic cancer regardless of degree of differentiation. RCK108 tended to be less stained in the prostatic cancer cells with lower grades of tumor differentiation compared to those with higher grades. 34 beta-E12 was stained only in the basal cells, but neither in the normal luminal cells nor the cancer cells. Using 34 beta-E 12, basal cells were positively stained in most of the cases with BPH, while not in PCA. Atrophic acini and AAH was stained with 34 beta-E12 as positively as BPH. Basal cells were discontinuously or negatively stained in many cases with high-grade PIN. CONCLUSIONS: The luminal cells in BPH were highly positively stained using 35 beta-H11 or RCK108. RCK108 tended to be less stained in the prostatic cancer cells with lower grades of tumor differentiation. Positive staining of 34 beta-E12 strongly suggested a benign lesion, therefore immunohistochemistry using this antibody would be useful as an aid for pathological diagnosis.     

Expression of cystatins,high molecular weight cytokeratin,and proliferation markers in prostatic adenocarcinoma and hyperplasia

BACKGROUND: Prostatic adenocarcinoma is the most common malignancy among men in the western world but the diagnostic and prognostic criteria for it are still not clearly defined. Additional means for its diagnosis and prognosis are clearly needed. Previously it has been shown that cystatin A is expressed in the basal cells of normal prostate and the expression disappears in prostatic carcinoma. METHODS: We have now studied the expression of both cystatins A and B in benign prostatic hyperplasias (BPH), prostatic intraepithelial neoplasias (PIN) and carcinomas of the prostatic epithelium and compared it with the expression of high molecular weight (HMW) cytokeratin as well as the proliferation markers cyclin A and Ki-67. The expression of the proteins was immunohistochemically assessed using 33 total prostatectomy specimens. RESULTS: Cystatin A was expressed in the basal cells in all cases of BPH, low-grade PIN, and high-grade PIN whereas carcinomas showed no staining of cystatin A. The 34 beta E12 cytokeratin expression was similar to basal cystatin A staining and was not seen in carcinoma foci. Cystatin B showed both nuclear and cytoplasmic expression in the columnar epithelial cells. The decrease in median cytoplasmic staining of cystatin B in carcinomas compared to other lesions was significant, but there was a significant increase in expression with dedifferentiation of carcinoma. Also cyclin A and Ki-67 staining were significantly different in non-carcinomatous foci compared to carcinoma foci and had a remarkably similar negative correlations with basal cystatin A and 34 beta E12 staining. CONCLUSIONS: The results show that cystatin expression can be used as an aid in the diagnosis of prostatic adenocarcinoma and especially cystatin A in the distinction between high grade PIN and grade I carcinoma.     

Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancer

BACKGROUND: Recent studies have demonstrated that peroxisome proliferator activator-receptors (PPAR)-gamma is expressed in some cancer cells such as breast, lung, and gastric cancer, and its ligand induces growth arrest of these cancer cells through apoptosis. However, the expression and localization of PPARs in prostate have not been examined. In this study, PPARs expression was investigated in human prostate cancer (PC), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues. METHODS: Tumor specimens were obtained from 156 patients with PC, 15 with PIN, 20 with BPH, and 12 patients with NP tissues. The expressions were investigated by RT-PCR and immunohistochemical methods. RESULTS: Immunoreactive PPAR-alpha and -beta were significantly apparent in PC tissues. Marked expressions of PPAR-alpha and -beta were also detected in PIN, BPH, and NP groups. However, very weak or no expression of immunoreactive PPAR-gamma was found in BPH and NP cases. In contrast, we found significant expression of immunoreactive PPAR-gamma in cancer cells in PC group and in PIN group. CONCLUSIONS: Our results demonstrated that PPAR-gamma is induced in PC, and suggest that PPAR-gamma ligands may mediate its own potent antiproliferative effect against PC cells through differentiation.     

Expression of the VEGF-receptor Flt-1 in benign, premalignant and malignant prostate tissues

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most potent regulators of angiogenesis and has been shown to act upon two tyrosine kinase family receptors: c-fms-like tyrosine kinase (Flt-1) and fetal liver kinase. Preliminary reports have emphasized that expression of VEGF receptors is endothelial cell-specific. In this study we verified the localization and distribution of Flt-1 protein and mRNA expression in prostatic adenocarcinoma (CaP) as well as prostate intraepithelial neoplasia (PIN) and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: 30 selected surgical specimens exhibiting areas with CaP, PIN and BPH histology were evaluated for Flt-1 protein expression by immunohistochemistry. Results were compared with tumor differentiation (Gleason-Score), serum-PSA and clinical followup. Flt-1 synthesis by prostatic carcinoma cell lines, freshly isolated BPH epithelial cells (BPH-EC) and stromal cells was investigated using RT-PCR and intron spanning primer. RESULTS: VEGF receptor Flt-1 specific anti-sera revealed significant staining of prostatic endothelial cells, but the reactivity was not restricted to endothelial cells. BPH-epithelial cells of all specimens reacted significantly with anti-Flt-1. In contrast, tumor cells failed to react with anti-Flt-1 in 56% of the specimens. BPH-EC revealed a uniform anti-Flt-1 reactivity, which was less pronounced and weaker in PIN. Loss of anti-Flt-1 reactivity of prostatic tumor cells did not correlate with preoperative PSA serum levels but increased with tumor dedifferentiation. Interestingly, tumor cells of all CaP specimens with a Gleason score of >8 exhibit no anti-Flt-1 immunoreactivity. Accordingly while PC3, DU145 and LNCaP cells were negative when tested using RT-PCR all BPH tissue derived BPH-EC revealed Flt-1 coding mRNA expression.CONCLUSIONS: Widespread distribution of VEGF receptor Flt-1 in BPH, PIN and prostate cancer specimens suggests that VEGF function in prostate is not restricted to endothelial cells and angiogenesis. However, since the receptor is lost in CaP cells and with tumor dedifferentiation, these yet unknown effects of VEGF on epithelial cells are obviously suppressed with malignant transformation.     

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.     

前列腺干细胞抗原在人前列腺癌组织中的表达及意义

目的　探讨前列腺干细胞抗原 (PSCA)在国人前列腺癌 (PCa)组织中表达的临床意义。　方法　采用免疫组织化学 (IHC)和核酸原位杂交 (ISH)方法检测 4 0例PCa、2 0例良性前列腺增生(BPH)和 2 0例前列腺上皮内瘤 (PIN)组织标本PSCA蛋白和mRNA表达 ,半定量法计算PSCA阳性表达细胞百分数和阳性表达强度 ,比较各组织间表达水平的差异及其与PCa分级、临床分期之间的关系。　结果　PCa、BPH、PIN组织PSCA中度阳性到强阳性表达分别为 85 % (34/ 4 0 )、2 0 % (4/ 2 0 )和35 % (7/ 2 0 ) ;PCa组织PSCA表达水平与BPH和PIN比较差异有统计学意义 (P <0 .0 5 ) ,BPH与PIN比较差异无统计学意义 (P >0 .0 5 ) ;PCa组织PSCA表达水平随Gleason评分及临床分期增加而升高。　结论　人PCa组织有PSCA蛋白质和mRNA的过表达 ,且与PCa病理分级、临床分期呈正相关 ,可能对PCa的诊断及判断预后有潜在价值。