前列腺癌中Bad蛋白的表达及其意义

目的探讨Bad蛋白在前列腺癌中的表达及其临床意义。方法选择前列腺癌和癌旁良性前列腺增生(benign prostate hyperplasia, BPH)各48例及21例前列腺上皮内瘤(prostate intraepithelial neoplasms, PIN),采用免疫组化SP法观察Bad蛋白在前列腺上皮及间质细胞中的表达,采用化学发光法检测血清PSA值,分析Bad蛋白与前列腺癌、PSA值的相关性。结果 Bad蛋白在前列腺癌和PIN中的阳性率分别为83.3%、66.7%,高于癌旁BPH的33.3%,差异有统计学意义(P均0.01);Bad蛋白在前列腺癌和BPH间质细胞中的阳性率分别为52.1%和25.0%,差异有统计学意义(P0.05);Bad蛋白在Gleason评分≤7和7的前列腺癌中阳性率分别为66.7%和92.6%,差异有统计学意义(P0.05);血清PSA值与Bad蛋白表达无相关性(P均0.05)。结论前列腺癌组织中Bad蛋白高表达,并与Gleason评分有关,提示Bad蛋白在前列腺癌的发生、发展中发挥重要作用。     

核仁素的表达定位和定量与前列腺癌演变的关系

目的探讨前列腺癌和非癌组织中核仁素表达定量和定位的差异,及核仁素表达的增高和核外迁移对鉴别诊断前列腺癌和非癌组织的价值。方法用免疫组化SP法检测50例前列腺癌组织和50例非癌组织中核仁素的表达,分析前列腺癌组织和非癌组织中核仁素表达定量和定位的差异,并比较核仁素与p504S和p63在前列腺癌中表达的相关性,分析前列腺癌中核仁素表达定量与癌组织Gleason评分的关系。结果前列腺癌和非癌组织中细胞核均表达核仁素;前列腺癌胞质和胞膜核仁素的阳性表达率(90%)明显高于癌旁正常前列腺组织(5%)、前列腺增生症(13%)和前列腺上皮内瘤变(20%)(P<0.01)。Allred半定量分析显示,前列腺癌组织中核仁素表达量(7.7±0.3)高于癌旁正常前列腺组织(3.9±0.2)、前列腺增生症(4.0±0.4)和前列腺上皮内瘤变(5.5±0.2)(P<0.01)。在前列腺癌中,核仁素胞质阳性表达与癌细胞p504S的阳性表达呈正相关,与基底细胞p63的阳性表达呈负相关(P<0.01)。前列腺癌中核仁素表达定量与Gleason评分呈正相关(P<0.01)。结论前列腺在癌变过程中核仁素表达增高,并出现核外迁移;核仁素的核外迁移...     

前列腺腺癌中双染鸡尾酒抗体Ki-67/caspase-3的表达及意义

目的探讨Ki-67/caspase-3鸡尾酒抗体在前列腺腺癌(PAC)、高级别前列腺上皮内瘤(HGPIN)及良性前列腺增生(BPH)组织中的表达及意义。方法收集40例PAC、30例HGPIN和BPH标本,按常规方法石蜡包埋,制作蜡块连续切片,进行HE染色及Ki-67/caspase-3鸡尾酒抗体双重免疫组化染色。结果 Ki-67表达阳性率及增殖指数在PAC组织中明显高于HGPIN和BPH组织,且随着Gleason分级增高其增殖指数存在递增趋势(P0.05,P0.01)。caspase-3在BPH组织中表达阳性率明显高于PAC及HGPIN组织(P0.05),但在PAC与HGPIN、不同Gleason分级PAC中的表达阳性率差异无统计学意义(P0.05)。Ki-67和caspase-3在PAC和HGPIN组织中的表达呈负相关,而在BPH中的表达呈正相关。结论 Ki-67/caspase-3在不同病变中表达不同,鸡尾酒抗体联合检测可用于前列腺良恶性疾病的诊断、鉴别诊断及预后的判断。     

前列腺相关疾病谱系中Glypican-1的表达及临床意义

目的 检测前列腺增生(prostatic hyperplasia, BPH)、前列腺上皮内瘤(prostatic intraepithelial neoplasia, PIN)和前列腺癌(prostate cancer, PCa)中磷脂酰肌醇聚糖-1(Glypican-1)的表达水平。方法 采用免疫组化、ELISA法检测Glypican-1在40例BPH、60例PIN及60例PCa中的表达,并复习相关文献。结果 Glypican-1在BPH和低级别前列腺上皮内瘤(low-grade prostatic intraepithelial neoplasia, LGPIN)中呈低表达,在高级别前列腺上皮内瘤(high-grade prostatic intraepithelial neoplasia, HGPIN)及PCa中呈高表达,平均秩次为46.10(BPH)、55.23(LGPIN)、89.75(HGPIN)、117.20(PCa),差异有统计学意义(P<0.001)。PCa组中血清学Glypican-1水平明显高于PIN组和BPH组(P<0.001),血清学Glypica...     

前列腺癌中EZH2 mRNA及蛋白表达与细胞增殖的关系

目的 探讨EZH2 mRNA和蛋白在前列腺癌中的表达及其与肿瘤细胞增殖的关系.方法 通过组织芯片技术,应用原位杂交和免疫组化方法检测48例前列腺癌中EZH2 mRNA和蛋白的表达以及Ki-67增殖指数,同时检测15例良性前列腺增生组织(BPH)和12例高级别上皮内瘤变(HGPIN)中EZH2 mRNA和蛋白的表达.结果 前列腺癌组织中EZH2蛋白和mRNA阳性率分别为87.50%和81.25%,均高于BPH和HGPIN,差异有显著性(P<0.05).EZH2蛋白与mRNA表达之间差异无统计学意义(P>0.05).EZH2蛋白的表达与Gleason分级、TNM分期相关(P<0.05),与患者年龄和术前血清前列腺特异抗原(PSA)水平无关(P>0.05).EZH2 mRNA的表达与TNM分期相关(P<0.05),与患者年龄、术前PSA水平及Gleason分级无关(P>0.05).EZH2蛋白表达程度与Ki-67细胞增殖指数呈明显正相关(r=0.746,P<0.05).结论 EZH2 mRNA及其蛋白在前列腺癌中表达上调,通过促进肿瘤细胞增殖使得肿瘤发生、发展,有望成为预测前列腺癌恶性程度进程的参考指标.     

前列腺癌雄激素受体表达与细胞凋亡的关系

目的：探讨前列腺癌雄激素受体与细胞凋亡的关系及其生物学特性,方法：56例前列腺癌和20例良性前列腺增生症,应用免疫组化方法检测石蜡蜡包埋的组织切片中雄激素受体（AR）表达和应用原位末端标记技术（TUNEL）检测细胞凋亡指数（AI）。结果：AR在良恶性前列腺组织中的表达差异无显著性（P＞0．05）。AR和AI与前列腺癌Gleason分级无关。AI在前列腺癌组织中的表达明显高于良性前列腺增生症（P＜0．05）,AR阳性的前列腺癌AI亦明显高于AR阴性的前列腺癌。结论：前列腺癌组织中AR的表达可诱导其细胞凋亡,并对前列腺癌的功能性分类和内分泌治疗的疗效判断具有实用的临床意义。     

前列腺癌骨转移灶中BMP-2、BMP-4、BMP-7的表达及临床意义

目的检测BMP-2、BMP-4、BMP-7在前列腺癌骨转移灶中的表达,探讨其在前列腺癌成骨性转移中的作用。方法采用免疫组化EnVision法检测28例前列腺癌骨转移病例及17例良性前列腺增生(benign prostate hyperplasia,BPH)病例中BMP-2、BMP-4、BMP-7的表达并对其进行对比分析。结果 BMP-2在所有前列腺癌骨转移灶及BPH病例中均表达,二者中其阳性率及表达强度无明显差异(P>0.05)。BMP-4在前列腺癌骨转移灶及BPH中的阳性率无明显差异(P>0.05),但在前者中BMP-4的表达强度明显高于后者(P<0.05)。BMP-7在前列腺癌骨转移灶中的阳性率及表达强度均明显高于BPH(P<0.05)。在BPH的阳性表达病例中,BMP-2、BMP-4、BMP-7细胞质与细胞核同时阳性的表达率分别为13.3%、7.1%和11.1%,在前列腺癌骨转移灶的阳性表达病例中,BMP-2、BMP-4、BMP-7细胞质与细胞核的同时阳性的表达率均为100%,且细胞核的表达强度明显高于细胞质。结论 BMP-4、BMP-7在前列腺癌骨转移灶中高表达,提示其在前列腺癌的成骨性转移中可能起重要作用。     

前列腺癌组织中N-Myc、p53的表达及其临床意义

目的探讨N-Myc、p53在前列腺癌组织中的表达、两者的相关性及其临床意义。方法收集2015～2016年安徽医科大学第一附属医院行前列腺手术的前列腺癌患者63例及前列腺增生(benign prostatic hyperplasia,BPH)患者50例,采用免疫组化MaxVision法检测病理组织中N-Myc、p53的表达。结果 N-Myc、p53在前列腺癌组织中的表达均升高(P 0. 05),前列腺癌组织中N-Myc、p53中表达与有无骨转移和TNM分期具有相关性(P 0. 05),与患者年龄、术前PSA水平等因素无关(P0. 05)。另外,p53表达与Gleason评分亦相关。结论 N-Myc和p53在前列腺癌中呈高表达,可能共同参与前列腺癌的恶性进展和转移,有望成为检测前列腺癌转移的新靶点。     

循环miRNA-141对前列腺癌的诊断和预后价值研究

 目的:研究血清miR-141在前列腺癌中的表达及临床意义。方法:采用实时荧光定量PCR检测75例前列腺癌和52例良性前列腺增生（BPH）患者,以及40例健康对照血清miR-141的相对表达水平。结果:前列腺癌血清miR-141的表达量较BPH和健康对照增高,差异有统计学意义（P＜0.01）。但miR-141在BPH组和对照组中的表达差异无统计学意义（P>0.05）。ROC曲线显示miR-141能够较好地区分前列腺癌与BPH（或健康对照）,曲线下面积分别为0.785（95%CI∶0.689～0.823）和0.801（95%CI∶0.723～0.868）。血清miR-141表达与Gleason积分、临床分期和骨转移相关（均P<0.05）,随着临床分期的增加,miR-141的表达水平增加;但miR-141表达量与患者年龄、肿瘤复发和血清前列腺特异性抗原水平无关(均P>0.05)。结论: 循环miR-141可作为非侵入性诊断前列腺癌并且判断其预后的分子标志物。     

新型前列腺特异膜抗原剪接变异体的发现及临床意义初步探讨

目的:探讨前列腺特异膜抗原（PSMA）及其与前列腺癌发生、发展的关系，寻求更为特异的前列腺癌诊断和治疗的靶点。 方法:采用RT-PCR和DNA测序技术，克隆PSMA基因新的剪接变异体，并根据其序列信息，设计特异性引物，检测其在不同病变前列腺组织及不同组织来源肿瘤细胞中的表达。 结果:发现了一种新的PSMA剪接变异体，其在前列腺癌、前列腺增生及正常前列腺组织中的表达率分别为92.6％、78.8％及10.0％，且特异表达于前列腺癌LNCaP细胞株，而在前列腺癌PC3细胞株、膀胱癌、肾癌、肝癌细胞株中均不表达。 结论:发现了一种新型PSMA剪接变异体（定名为PSMA5），并证实该变异体与前列腺癌及前列腺增生有明显相关性，为研究前列腺癌的发生机制和寻求前列腺癌特异性诊治靶点提供了新的线索。     

Expression of androgen receptor and growth factors in premalignant lesions of the prostate

Analysis of growth factors and receptors in putative premalignant lesions of prostatic adenocarcinoma should aid our understanding of their growth pathways. Sixty prostatic TURP (transurethral resection of the prostate) specimens exhibiting atypical adenomatous hyperplasia (AAH) and/or prostatic intraepithelial neoplasia (PIN) lesions were assayed by immunohistochemistry for androgen receptor (AR), epidermal growth factor receptor (EGFR), c-erbB-2, transforming growth factor-alpha (TGF-α), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), MIB-1, E-cadherin, and high molecular weight keratin. Expression of these factors in the lesions was compared with that in the co-existing benign prostatic hyperplasia (BPH) or prostatic adenocarcinoma. Strong AR nuclear staining was observed in the luminal cells, but not the basal cells, of BPH and PIN lesions and in all the carcinomas examined. A similar growth factor and receptor profile was demonstrated in the secretory epithelium of high-grade PIN and carcinoma with a tendency to higher expression of membranous EGFR and c-erbB-2 and cytoplasmic TGF-α, and lower levels of FGF-2 than in low-grade PIN or BPH glands. Also, increased rates of proliferation, as estimated by MIB-1 stained cells, were observed in high-grade PIN in comparison with low-grade PIN and BPH and were not confined to the basal layer. AAH lesions resembled neither BPH nor carcinoma. Proliferation was virtually absent (MIB-1 expression); both AR and E-cadherin expression was significantly reduced; and, with the exception of FGF-2, all the other growth factors and receptors studied were absent. The results presented would support a premalignant role for high-grade PIN, whilst AAH would appear to represent a quiescent phenotype unlikely to progress to neoplasia. Copyright © 1998 John Wiley & Sons, Ltd.     

前列腺疾病中TK1和Ki-67的表达

目的通过对前列腺癌、前列腺上皮内瘤变、前列腺良性增生及其正常前列腺组织中胸苷激酶1（TK1）和细胞增殖蛋白（MIB-1）标记Ki-67的表达，探讨其对前列腺癌的治疗、预后所起的作用。方法采用免疫组化ABC法检测前列腺癌（PCa）42例，前列腺上皮内瘤变（PIN）35例，良性前列腺增生（BPH）25例和正常前列腺（NP）组织10例中TK1及Ki-67的表达。结果良性前列腺增生及正常前列腺组织中几乎检测不到增殖细胞，在前列腺上皮内瘤中增殖细胞所占的百分比大约为16％～17％，在前列腺癌组织中TK1阳性表达率57．1％，高于Ki-67阳性表达率（47．6％，P〈0．05）。结论TK1不仅同Ki-67一样，可作细胞增殖的指标，还因其参与DNA合成及细胞间“旁观者效应”等原因，从而给临床提供治疗及预后方面有价值的参考。     

Down-regulation of drs mRNA in human prostate carcinomas

We have previously reported that the drs gene has the ability to suppress transformation by v-src and v-K-ras in the rat cell line F2808. We have also shown that the expression of drs mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that down-regulation of drs mRNA is correlated with the development of human cancers. To clarify the role of the drs gene in prostate carcinogenesis, we examined the expression of the drs gene in 3 normal prostate, 13 prostate carcinoma, 5 benign prostate hyperplasia (BPH), and 2 prostatic intraepithelial neoplasia (PIN) tissue specimens by in situ hybridization and in 3 prostate carcinoma cell lines (PC3, LNCaP, and DU145) and 2 BPH tissues by Northern blot analysis. Furthermore, the deletion, and rearrangement of the drs gene were analyzed by Southern blot analysis. The drs mRNA was significantly expressed in normal prostate and BPH tissues, whereas it was markedly down-regulated in prostate carcinoma tissues and prostate carcinoma cell lines. In 2 tissues from PIN, drs mRNA was weakly expressed. There were no differences between prostate carcinoma cell lines and BPH tissues in terms of their banding patterns of Southern blot analysis. These results indicate that down-regulation of drs mRNA is closely correlated with development of prostate carcinoma, suggesting a tumor-suppressor function of the drs gene in this cancer.     

Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by Immunohisto-chemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsln enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmlc localization of the protein in cells.     

Precursor lesions to prostatic adenocarcinoma

High-grade prostatic intraepithelial neoplasia (PIN) is the one well-documented precursor to adenocarcinoma of the prostate. This review article defines both low- and high-grade PIN. Unusual variants of high-grade PIN are illustrated. Benign lesions that may be confused with high-grade PIN, including central zone histology, clear cell cribriform hyperplasia, and basal cell hyperplasia are described and illustrated. High-grade PIN is also differentiated from invasive acinar (usual) and ductal adenocarcinoma. The incidence of high-grade PIN, its relationship to carcinoma (including molecular findings), and risk of cancer on rebiopsy are covered in detail. Finally, intraductal carcinoma of the prostate, a controversial entity, is discussed and differentiated from high-grade PIN.     

β4整合素在前列腺各组织中的表达及意义

目的　探讨 β4 整合素在前列腺各组织中的表达及意义。方法　将 10 0例诊断明确的前列腺标本分为五组 ,即正常组 (NP)、良性前列腺增生组 (BPH)、高级别上皮内瘤组 (HPIN)、偶发癌组 (PIC)及前列腺癌组 (PC) ,每组 2 0例。应用免疫组化SP法检测 β4 整合素在以上五组标本中的表达情况。结果　β4 整合素在NP、BPH、HPIN、PIC及PC组织中的表达是逐渐降低的 ,BPH组表达明显强于HPIN组 ,其差异有显著意义 (P <0 .0 5 ) ,HPIN组和PIC组的表达无显著差别 (P >0 .0 5 )。结论　β4 整合素与前列腺癌发生、发展密切相关。     

前列腺摘除病检和穿刺活检的形态学差异

目的：探讨前列腺摘除病检和穿刺活检的形态学差异。方法：对340例穿刺标本和280例因良性前列腺增生（BPH）而摘除的前列腺标本进行形态学对比分析。结果：在穿刺活检中,前列腺癌,上皮内新生物（PIN）和非特异性肉芽肿性前列腺炎（NSGP）的检出率明显高于摘除者,在前列腺摘除的标本中,梗死,磷化,间质增生性结节,腺性尿道炎和非典型性腺瘤样增生（AAH）的检出率明显市政地穿刺活检,结论：形态学差异是由于穿刺和摘除标本分别取自前列腺不同解剖并且并且部位所致,对穿刺和摘除前列腺的病理诊断,应该有不同的鉴别诊断思路。     

Decreased annexin I expression in prostatic adenocarcinoma and in high-grade prostatic intraepithelial neoplasia

AIMS: To analyse annexin I expression in prostatic carcinoma. Annexin I belongs to a family of structurally related calcium and phospholipid-binding proteins implicated in signal transduction, DNA replication, cell proliferation and apoptosis. The decreased expression of annexin I, II and VII proteins has been reported in different types of cancer. METHODS AND RESULTS: Using immunohistochemistry, we analysed annexin I expression in 77 cases of prostatic adenocarcinoma (Gleason score 6, N = 40; Gleason scores 7-8, N = 27; and Gleason scores 9-10, N = 10) and high-grade prostatic intraepithelial neoplasia (PIN, N = 50). Immunoreactivity of annexin I in tumour cells was evaluated as negative (< 5% of cells), focally positive (5-25% of cells) or positive (> 25% of cells). In contrast to positive staining in adjacent benign prostatic epithelium, annexin I expression was decreased (focally positive) in 76% of cases of high-grade PIN (P < 0.0001) and was decreased or absent in 81% of prostatic adenocarcinomas (P < 0.0001). Annexin I expression in all higher grade tumours (Gleason scores 7-10) was only focally positive or absent. CONCLUSIONS: Expression of annexin I inversely correlates with the increasing histological grade of prostatic adenocarcinoma. By showing a progressive loss of annexin I expression in high-grade PIN, intermediate-grade and high-grade cancer, our findings suggest that the loss of annexin I expression occurs early in prostatic tumorigenesis and becomes more prominent throughout tumour progression. The loss of expression of annexin I may serve as a useful marker of prostate cancer development and progression.     

Immunohistochemical study of the expression of epidermal growth factor receptor in benign prostatic hypertrophy, prostatic intraepithelial neoplasia and prostatic carcinoma

The present study provides an analysis of immunohistochemical expression and localization of epidermal growth factor receptor (EGFR) in formalin fixed paraffin embedded specimens of prostate. Thirty-five cases each of benign prostatic hypertrophy (BPH) and prostatic carcinoma and 30 cases of prostatic intraepithelial neoplasia (PIN) were taken up for study. Streptavidin biotin peroxidase method was employed for immunohistochemical staining. EGFR positivity was observed in all the cases (100%) of BPH and PIN and in only 10 cases (28.5%) of prostatic carcinoma. In both BPH and PIN the basal cells revealed significantly higher intensity and percentage cell positivity than the luminal cells. Intensity and percentage of positively stained basal cells in BPH was higher than PIN basal cells but the difference was not statistically significant. The intensity and percentage cell positivity of BPH basal cells and PIN basal and luminal cells were significantly greater than the epithelial cells of prostatic carcinoma. Presently, the significance of variable expression of EGFR in various types of prostatic lesions is unknown.     

Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers

Prostate-specific membrane antigen (PSMA), a type II transmembrane metallo-peptidase highly overexpressed in prostate cancer cells, has been studied as a targeting molecule in prostate cancer. Recently, PSMA has also been found to be expressed in the neovasculature of multiple nonprostatic solid tumors. Because of its unique expression pattern limited to tumor-associated endothelial cells, PSMA may also be an interesting molecule for vascular targeting. In this study, PSMA expression was determined by immunohistochemistry in 119 cases of primary gastric adenocarcinoma, 130 cases of primary colorectal adenocarcinoma, and 24 metastasis of colorectal adenocarcinoma. Expression data were correlated with clinicopathologic information. PSMA expression was detected in tumor-associated neovasculature of 79 (66%) of 119 gastric and 110 (85%) of 130 colorectal carcinomas. Furthermore, the neovasculatures of 16 (84%) of 19 liver and 4 (80%) of 5 nodal metastases from colorectal carcinomas were prostate-specific membrane antigen positive. There was a trend for high-grade tumors to higher PSMA expression (Spearman r = 0.18, P = .046) in colorectal cancers. No association between PSMA expression and overall- or disease-free survival was observed in gastric or colorectal cancers. This study provides the first in-depth look at PSMA expression in gastric and colorectal cancer. Because of its highly tumor-restricted expression and its accessibility to targeted therapy, PSMA represents a promising therapeutic and diagnostic target in colorectal and gastric cancer.