前列腺癌PCNA检测及其意义的探讨

选用抗ＰＣＮＡ单克隆抗体、采用免疫组化ＡＢＣ法检测了３０例前列腺增生（ＢＰＨ）和前列腺癌（ＰＣ）石蜡标本中ＰＣＮＡ的表达。结果表明ＰＣＮＡ阳性细胞百分率：ＢＰＨ组为２７．５％±４．２％．ＰＣ组为４９．６％±８．９％，其中伴神经内分泌（ＮＥ）分化ＰＣ组为５７．０％±５．３％，不伴ＮＥ分化为４５．２％±７．９％。统计结果显示伴ＮＥ分化ＰＣ组ＰＣＮＡ阳性细胞百分率明显高于ＢＰＨ组（Ｐ＜０．０５）。在１４例ＰＣ存活者中，ＰＣＮＡ阳性细胞百分率低者存活时间长于百分率高者，提示ＰＣＮＡ可能将成为ＰＣ患者内分泌治疗预后的重要指标     

性激素受体在前列腺病变组织中的表达

用抗雄、雌及孕激素受体（ＡＲ、ＥＲ和ＰＲ）的多克隆抗体，采用ＡＢＣ法检测３０例良性前列腺增生（ＢＰＨ）和３０例前列腺癌（ＰＣ）石蜡标本中性激素受体（ＳＲ）的表达。结果显示：ＢＰＨ组和ＰＣ组ＡＲ、ＥＲ和ＰＲ表达的阳性率差异均无显著性，因而不能根据ＡＲ、ＥＲ和ＰＲ阳性率区分ＢＰＨ和ＰＣ。另外，ＡＲ、ＥＲ或ＰＲ阳性者的存活时间均长于ＳＲ阴性者，提示ＳＲ表达与ＰＣ患者内分泌治疗的预后有一定关系，受体阳性率     

钙调素拮抗剂对HeLa细胞S期进程的影响

目的　探讨钙调素拮抗剂三氟拉嗪（ＴＦＰ）对ＨｅＬａ细胞Ｓ期进程的影响及其分子机理。　方法　通过ＴｄＲ双阻断法获得同步化的Ｓ期ＨｅＬａ细胞,以３Ｈ－ＴｄＲ掺入法和Ｗｅｓｔｅｒｎ 技术分别观察了ＴＦＰ对ＨｅＬａ 细胞Ｓ期进程和胸苷激酶（ｔｈｙｍ ｉｄｉｎｅ ｋｉｎａｓｅ,ＴＫ）活性及细胞周期引擎分子ＣｙｃｌｉｎＡ、Ｃｄｋ２ 和细胞周期调节蛋白ｐ８０ｃｄｃ２５Ｂ、ＰＣＮＡ、ｐ２１ 蛋白表达水平的影响。　结果　ＴＦＰ（２０μｍ ｏｌ／Ｌ）能使３ Ｈ－ＴｄＲ的掺入峰值后移,并抑制了Ｃｙ－ｃｌｉｎＡ、ＰＣＮＡ、ｐ８０ｃｄｃ２５Ｂ的表达和提高了ｐ２１ 蛋白的水平,但对Ｃｄｋ２的表达几乎无影响。　结论　ＣａＭ 除了能通过影响ＰＣＮＡ的水平直接作用于ＤＮＡ 合成,同时又可通过作用于ＣｙｃｌｉｎＡ、ｐ８０ｃｄｃ２５Ｂ、ｐ２１ 等周期引擎分子和调控因子水平正调ＨｅＬａ 细胞Ｓ期进程。     

良性增生前列腺组织及上皮和间质细胞中r—GT活性及GSH含量…

本文报道测定正常人和良性腺增生症（ＢＰＨ）患者前列腺组织匀浆、上皮及间质细胞中ｒ－谷氨酰转肽酶（ｒ－ＧＴ）活性及其底物还原型谷脱甘肽（ＧＳＨ）的含量。结果显示：①ＢＰＨ组织匀浆、上皮及间质细胞中ｒ－ＧＴ活性显著升高，分别为正常前列腺相应组分的４．５、３．２和４．１倍，而ＧＳＨ含量则明显降低；②正常及ＢＰＨ组织上皮细胞中ｒ－ＧＴ活性均显著高于相应间质细胞，而ＧＳＨ含量则低于间质细胞。提示ｒ－ＧＴ活性     

p53、c-erbB-2、PCNA和EGFR在膀胱癌中过表达及其意义

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌中异常表达与病理分级、临床分期、复发和预后的关系。方法：应用免疫组化Ｓ－Ｐ法检查１１７例膀胱移行细胞癌组织中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ的表达水平。结果：１１７例膀胱移行细胞癌中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ阳性表达率分别为４７．０％、２９．９％、５３．８％和４８．７％。ｐ５３和ＰＣＮＡ阳性表达产物定位于肿瘤细胞核内，ｃ－ｅｒｂＢ－２阳性表达产物定位于细胞膜上，ＥＧＦＲ阳性表达产物定位于细胞膜或细胞浆内。结果表明ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达与膀胱癌的分级、分期、复发及术后生存率等之间有统计学意义。结论：ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达有助于评估膀胱癌预后，多基因异常表达作为预后评价指标更有意义。     

乳腺导管原位癌病理形态及c-erbB-2、p53和PCNA表达

目的：对乳腺导管原位癌进行病理形态分析，并行ｃ－ｅｒｂＢ－２、ｐ５３癌基因蛋白、增殖细胞核抗原（ＰＣＮＡ）表达以及相关性的研究，以期为临床判断潜在恶性程度及预后提供参考指标。方法：运用病理形态分析以及枸橼酸－微波－ＡＢＣ免疫组化法对２５例常规福尔马林固定、石蜡包埋乳腺导管原位癌组织进行回顾性研究。结果：（１）２５例乳腺原位导管癌ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率分别为３６．０％，４０．０％和４０．０％；（２）粉刺型ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率均高于非粉刺型，而且ｃ－ｅｒｂＢ－２阳性率相差有显著性（Ｐ＜０．０５）；（３）坏死、核异型性、核分裂数与ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ的表达有关，其中，坏死与ＰＣＮＡ阳性表达显著相关（Ｐ＜０．０５），核异型性与ｃ－ｅｒｂＢ－２蛋白表达显著相关（Ｐ＜０．０５）。结论：乳腺导管原位癌无论病理形态还是生物学行为都是异质性的，除了组织学亚型，某些形态指标以及ｃ－ｅｒｂＢ－２癌基因蛋白的表达也可作为恶性度指标。     

癌基因c—erbB—2在胆囊癌中的异常表达及意义

本文应用免疫组织化学ＡＢＣ方法，对３６例胆囊癌组织标本进行了癌基因ｃｅｒｂＢ２的测定，同时进行了增殖细胞核抗原（ＰＣＮＡ）的测定，作为反映ｃｅｒｂＢ２的表达与胆囊癌细胞增殖状态关系的指标，结果３６例胆囊癌组织中，１４例（３８．８８％）显示ｃｅｒｂＢ２基因过度表达；２２例（６１．１１％）显示ＰＣＮＡ高表达，其中１２例两种标记同时阳性。半定量分级，Ｓｐｅａｒｍａｎ秩相关分析表明，两者呈显著相关（Ｐ＜０．０１）；ｃｅｒｂＢ２基因表达的程度与胆囊癌的组织学类型有关。本文结果提示，胆囊癌中有ｃｅｒｂＢ２基因的异常表达并可能有病因学意义；ｃｅｒｂＢ２基因的表达情况可有效地反映胆囊癌的生物学特性，作为衡量胆囊癌分化程度、判断患者预后的有用指标     

bcl-2、p53蛋白及PCNA表达与横纹肌肉瘤临床病理相关性研究

目的：研究横纹肌肉瘤（ＲＭＳ）中ｂｃｌ－２、ｐ５３、ＰＣＮＡ表达与其临床病理的相关性。方法：对５０例（随访４１例）横纹肌肉瘤进行免疫组化ＡＢＣ法标记。结果：ｂｃｌ－２、ｐ５３基因蛋白和ＰＣＮＡ，发现ｂｃｌ－２、ｐ５３、ＰＣＮＡ阳性表达率分别为２８％、７２％、７０％，其阳性表达与年龄、性别及不同组织类型的ＲＭＳ无关（Ｐ＞０．０５）。但与分化程度有关，ｐ５３、ＰＣＮＡ在低分化ＲＭＳ阳性率分别为８５％、９５％，显著高于高分化ＲＭＳ４２．８％和１４．３％（Ｐ＜０．０５），随访存活１年以内的ｐ５３、ＰＣＮＡ阳性率均为８６．７％，亦明显高于存活超过３年以上的阳性率３３．３％和４１．７％（Ｐ＜０．０５）。而ｂｃｌ－２在低分化ＲＭＳ阳性２０％显著低于高分化７１．４％（Ｐ＜０．０５），随访存活１年以内的阳性率１３．４％明显低于存活超过３年以上的４１．４％（Ｐ＜０．０５）。ｐ５３与ｂｃｌ－２阳性表达呈明显负相关，ｐ５３阳性率越高，而ｂｃｌ－２阳性率越低。结论：ＰＣＮＡ、ｐ５３、ｂｃｌ－２蛋白表达能比较准确地反映ＲＭＳ的生物学特性，ｐ５３、ｂｃｌ－２可作为肿瘤预后显著相关的有效指标。     

正常前列腺和良性前列腺增生(BPH)凋亡和增殖区的变化

目的　通过对瘤蛋白Ｂｃｌ－２在前列腺中拮抗细胞死亡的变化过程和范围以及表达情况的研究,从而得出细胞凋亡和增殖二者失衡导致良性前列腺增生（ＢＰＨ）的结果。方法　从尸体解剖中获取１０例正常前列腺标本（平均年龄４３．７岁）作对照,３０例有症状行前列腺切除的前列腺瘤标本（平均年龄６１．４岁）,组织经福尔马林固定,石腊包埋切片。增殖细胞和Ｂｃｌ－２的表达分别以Ｍｉｂ－１和抗－Ｂｃｌ－２抗体行免疫组化染色,凋亡小体用特殊的原位杂交技术染色,光镜下确定细胞分布的百分比。结果　正常前列腺外周区上皮细胞增殖和凋亡…     

HBcAg/HBeAg对慢性乙型肝炎患者PBMC中Th1/Th2类细胞应答的影响

目的 探讨ＨＢｃＡｇ／ＨＢｅＡｇ对慢性乙型肝炎患者ＰＢＭＣ中Ｔｈ１／Ｔｈ２类细胞应答的影响。方法 用套式ＰＣＲ法检测６４便慢性ＨＢＶ感染者ＰＢＭＣ中ＨＶＢ ＤＮＡ;分别用ＰＨＡ、ＨＢｃＡｇ和ＨＢｅＡｇ体外培养;ＥＬＩＳＡ法检测ＰＢＭＣ产生Ｔｈ１类细胞因子（ＩＬ－２、ＩＦＮ－γ）和Ｔｈ２类细胞因子（ＩＬ－４、ＩＬ－１０）的含量。结果 表明ＨＢＶ ＤＮＡ阳性组和阴性组相比,无论是在ＰＨＡ还是在ＨＢｃＡ     

前列腺病变组织中细胞凋亡与bcl-2、bax、PCNA表达

目的　研究前列腺良、恶性病变组织中细胞增殖与凋亡及其与相关蛋白表达意义。方法　采用原位细胞凋亡标记技术 (TUNEL)及免疫组织化学ABC法对 36例前列腺癌 (PCa)、2 0例前列腺增生 (BPH)和 11例正常前列腺 (NP)组织石蜡切片bcl 2、bax、PCNA蛋白及细胞凋亡检测。结果　前列腺癌细胞凋亡指数 (AI)高于BPH和NP(P <0 0 1) ,bcl 2蛋白阳性表达者AI低于阴性者 (P <0 0 1) ,bax蛋白阳性表达者AI高于阴性者 (P <0 0 5 ) ;前列腺癌和BPH的bcl 2和PCNA蛋白阳性表达率高于NP(P <0 0 5 ) ,并随着肿瘤分级增高而增高 ;NP、BPH和前列腺癌的bax蛋白阳性表达率差异无显著性。前列腺癌细胞增殖指数 (PI)明显高于BPH(P <0 0 1) ,BPH细胞PI较NP明显增高 ,但细胞AI却显著下降。结论　细胞增殖与细胞凋亡的增加在PCa的发生和发展中起到了重要作用。在BPH的形成过程中前列腺组织细胞增殖增加而细胞凋亡减少 ,其中bcl 2和bax在细胞凋亡调节中起重要作用。     

Immunohistochemical analysis of the impact of ischemic change in benign prostatic hyperplasia

ObjectiveWe conducted experiments to elucidate the impact of ischemic change on benign prostatic hyperplasia (BPH) using immunohistochemistry.MethodsMedical records of consecutive patients over 60 years of age who underwent transurethral resection of the prostate for BPH between January 2009 and September 2012 were evaluated. As vascular risk factors, the presence or absence of diabetes mellitus, hypertension, current smoking, obesity, dyslipidemia, and diseases related to bladder function were investigated. As BPH-related factors, International Prostate Symptom Score, quality of life, maximal flow rate, postvoid residual volume, prostate-specific antigen, prostate volume, prostate calculi, and medication state for BPH were investigated. Immunohistochemistry was performed for hypoxia-inducible factor (HIF-1α), sex hormone receptors, and smooth muscle actin. Additionally, microvessel density (MVD) and diffuse fibrosis (DF) were evaluated.ResultsA total of 101 patients were included and HIF-1α expression in stroma and glands were observed in 56 (55.4%) and 34 (33.7%) cases, respectively. There was no significant association between HIF-1α expression and vascular risk factors or BPH-related variables. However, there was a significant correlation between the HIF-1α expression in stroma and higher MVD. HIF-1α expression in the stroma was also significantly correlated with higher expressions of the androgen and progesterone receptors in the stroma. DF was frequently found in cases with higher HIF-1α expression in the stroma than in those with lower HIF-1α expression.ConclusionIn patients with response to ischemic changes of the prostate, HIF-1α expression could be confirmed, and the expression of the androgen receptor was significantly lower in these patients. Chronic ischemic damage in the prostate can progress to a condition that is refractory to pharmacologic therapy. Chronic ischemic damage, which can progress to refractory phase to pharmacologic therapy, is correlated with the hormonal status of prostate.     

Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate

Interleukin-6 (IL-6) and its receptor have been implicated in prostate cancer progression. Because other members of the IL-6 family such as leukaemia inhibitory factor (LIF) and oncostatin M (OSM) share gp130, the signal transduction subunit of their receptors, interpretation of the data without considering the expression of these cytokines and their specific receptor subunits could be misleading. The immunohistochemical pattern of the IL-6 family and their receptor subunits in normal prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PC) was investigated. In normal prostates, gp130 and OSMRalpha were detected exclusively in the stroma and LIFRbeta was very scarce. While IL-6 was scarcely immunolocalized to the basal cells of the epithelium, OSM was detected in the stroma and LIF in both the epithelium and the stroma. This suggests an autocrine role for this family of cytokines in the stroma of normal prostates. In BPH, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, whereas LIFRbeta was localized only to the epithelium. IL-6 localized preferentially to the epithelium, OSM to the stroma, and LIF to both compartments. Therefore, in addition to the autocrine role in the stroma, IL-6 and OSM may play a paracrine role from the stroma to the epithelium in BPH. In PC, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, increasing with rising Gleason grade, whereas LIFRbeta was localized exclusively to the epithelium of low Gleason grade carcinomas. IL-6, LIF, and OSM localized in all cell types, with immunostaining increasing with Gleason grade. These data suggest an autocrine role for these cytokines in the epithelial cells of PC. The distinct pattern of expression of LIFRbeta exclusively in low Gleason grade carcinomas makes LIFRbeta a candidate for malignancy diagnosis. The role of OSM mainly in high Gleason grade carcinomas makes OSM a putative target for prostate cancer therapy.     

IL-2, its receptors, and bcl-2 and bax genes in normal, hyperplastic and carcinomatous human prostates: immunohistochemical comparative analysis

The presence of interleukin-2 (IL-2) and its receptors (Ralpha, Rbeta, Rgamma), and their relationship with the products of bcl-2 and bax genes was studied in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by ELISA, Western blot, and immunohistochemistry. A comparative semiquantitative immunohistochemical study was also performed. For all the antibodies assayed, immunoreactions were found in the epithelium and some stromal cells in the three types of specimens studied. These immunoreactions were much more higher in PC samples than in normal prostates. In BPH, immunoreactions were similar to that of normal prostates (bax), similar to that of PC (IL-2 and its three receptors), or intermediate between that of normal prostates and that of PC (bcl-2). Immunoexpressions of IL-2 and its receptors were found in the epithelial basal cells and some stromal cell of normal prostates and might be related to the control of the proliferation-apoptosis equilibrium. The increased expressions of IL-2 and its receptors in the epithelium of prostates in BPH, associated with increased bcl-2 expression which would account for the decrease in the apoptosis index that has been reported in this disorder. The increased expression of both bcl-2 and bax in PC might be involved in the higher apoptosis index reported in PC specimens. Since IL-2 administration seems to have an anti-tumour effect, the increased expression of this interleukin in BPH and PC could be interpreted as an attempt to hinder cell proliferation which would only be efficient at high doses.     

C-erbB-2、P~(53)和PCNA在前列腺癌中的表达及其意义

目的研究前列腺癌及前列腺增生症组织中C-erbB-2和P53PCNA表达的关系及其临床意义。方法采用免疫组织化学方法检测31例前列腺增生及69例前列腺癌患者C-erbB-2、P53和PCNA的表达水平。结果①C-erbB-2和P53在前列腺癌的阳性率分别是56.52%和69.56%,均高于良性前列腺增生的阳性率,但差异无统计学意义(P>0.05),②在前列腺癌中,低分化组C-erbB-2的表达水平明显高于高、中分化组,差异有统计学意义(P<0.05);③P53表达水平在上述各组之间差异均有统计学意义(P<0.05);④PCNA在前列腺癌组织中表达较前列腺良性增生症组织中增加,差异有统计学意义(P<0.001);PCNA的表达随着组织学分级及临床分期的增加而增加(P<0.001),PCNA高表达组术后生存率明显低于低表达组(P<0.01)。结论P53蛋白表达与肿瘤的分级和分化无统计学意义,而前列腺癌C-erbB-2和PCNA蛋白的表达异常增高,可能与前列腺癌的发生发展有关,联合检测PCNA和C-erbB-2对其肿瘤的恶性程度、生物学行为及预后评估有着重要意义。     

碱性成纤维细胞生长因子在前列腺增生和癌组织中表达的临床意义

目的 :探讨碱性成纤维细胞生长因子 (b FGF)在前列腺增生和前列腺癌组织中表达的临床意义。方法 :采用斑点杂交技术和免疫组化染色 ,测定 40例正常前列腺 (NP)、3 8例前列腺增生症 (BPH )和 3 6例前列腺癌组织 (Pca)中b FGF的表达。结果 :BPH和Pca组织中 ,b FGF的表达明显高于NP组织 (P <0 .0 1)。b FGF表达升高的程度与BPH的分度、Pca的病理分级和临床分期均无明显关系。结论 :b FGF可能为BPH和Pca组织自身分泌 ,与其发生发展过程密切相关     

The relation of beclin 1 and bcl-2 expressions in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: A tissue microarray study

The aim of the present study was to evaluate the expressions of beclin 1 and bcl-2 in prostate cancer (PC) and high grade prostatic intraepithelial neoplasia (HGPIN), and to investigate their relationship with clinicopathological parameters. The study included 30 benign prostatic hyperplasia (BPH), 40 HGPIN and 106 primary PC cases. The expressions of beclin 1 and bcl-2 were assessed semiquantitatively based on both the percentage and intensity of positive staining cells. Beclin 1 was positive in 27 (90%) BPH, 37 (92.5%) HGPIN, and 90 (84.9%) PC cases (p > 0.05). Bcl-2 immunostaining was detected in 99 (93.4%) PC, 37 (92.5%) HGPIN, and 9 (30%) BPH cases (p < 0.0001). Regarding expression scores, beclin 1 was significantly lower in PC cases than in the HGPIN and BPH groups (p < 0.0001), and it was also negatively correlated with Gleason score (p = 0.004, r = −0.274). Bcl-2 expression score was significantly higher in PC than in the other groups (p < 0.0001), and also positively correlated with Gleason score (p < 0.0001, r = 0.425). Furthermore, a negative correlation was found between bcl-2 and beclin 1 expression scores in PC cases (p = 0.006, r = −0.265). Our results suggest an association between bcl-2 and beclin 1 expressions in malignant transformation of prostate tissue and also in regulating PC cell differentiation, progression and the aggressiveness of PC.     

前列腺增生组织中间质细胞增殖和表型转化与雌激素受体α表达的关系

目的 比较人正常前列腺(NP)和前列腺增生(BPH)中间质细胞标记蛋白、增殖细胞核抗原(PCNA)和雌激素受体α(ERα)的表达差异,并检测BPH组织间质细胞标记蛋白与PCNA或ERα同时呈阳性染色的细胞.方法 对4例NP和8例BPH连续切片应用免疫组织化学方法,观察波形蛋白(vimentin)、α-平滑肌肌动蛋白(α-SMA)、肌球蛋白(myosin)、PCNA和ERa的表达定位.结果 与NP相比在BPH中,α-SMA阳性染色细胞显著增加;波形蛋白在间质中阳性染色细胞有所增加,在腺泡基底层及临近腺泡外层间质中阳性染色细胞明显增加;在临近腺泡外的数层间质细胞中肌球蛋白和ERα由部分阳性变为完全阴性染色,而在远离腺泡的间质中其阳性染色细胞由散在斑块状分布变为簇状密集排列;PCNA在间质中阳性染色细胞有所增加,在基底细胞层中阳性染色细胞显著增加.连续切片免疫组织化学染色显示,在腺泡上皮基底层存在PCNA与波形蛋白、ERα共定位的细胞;在间质中存在肌球蛋白与ERα共定位的细胞.结论 与NP相比,BPH间质细胞表型发生明显变化,且其增殖和表型转化与ERα表达定位的改变密切相关.     

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。