ER、AR在前列腺穿刺活检组织中的表达及临床病理意义

目的探讨雌激素受体、雄激素受体在前列腺穿刺活检组织中的表达及临床意义。方法选择2014-01—2016-12间在惠州市中心人民医院行穿刺活检确诊为前列腺癌的144例组织学标本作为实验组,60例前列腺增生标本作为对照组。采用免疫组化染色分析其雌激素受体、雄激素受体、34βE12及P63的表达情况。结果 ER、AR、34βE12及P63在BPH中阳性表达率分别为35.00%、68.33%、96.67%、91.67%,在PCa中阳性表达率分别为40.28%、53.47%、0%、0%,ER、AR在BPH和PCa中表达差异无统计学意义(P0.05)。ER在分级分组中的第2组PCa患者中呈高表达,AR在分级分组中的第1组PCa患者中呈高表达,差异均有统计学意义(P0.05)。144例PCa患者中,ER阳性58例,其中AR阳性45例;ER阴性86例,其中AR阴性54例。PCa患者的ER与AR表达密切相关(P0.01)。结论部分前列腺癌患者表达ER、AR,且ER、AR阳性较易出现在分级分组较低的患者,ER、AR在前列腺癌中的表达呈正相关。联合检测ER、AR、34βE12及P63可为低分组前列腺癌的穿刺活检诊断及鉴别诊断提供参考指标,提高早期诊断阳性率及准确性。     

雄激素受体在乳腺癌患者预后中的价值

目的 以淋巴结转移及c-erbB2表达情况作为病例分组依据,探讨雄激素受体(AR)在乳腺癌预后中的价值.方法 回顾性分析2003年1月至6月连续收治的原发性女性乳腺癌患者184例,收集其临床资料,采用免疫组化方法检测化疗前乳腺癌组织的雌激素受体(ER)、孕激素受体(PR)、AR、c-erbB2蛋白表达,以淋巴结状况及c-erbB2蛋白表达情况分组,探讨AR表达与淋巴结状况、c-erbB2蛋白表达的关系及AR对生存率的影响.结果 184例均获随访5年以上,随访率100%.全组淋巴结转移率为45.1%,5年远处转移率为16.9%,5年生存率为86.4%.将184例分为淋巴结阴性及受累两组,x2检验表明AR表达情况与淋巴结状况低度相关(P＜0.05,r,=-0.236),淋巴结阳性者AR表达率低.Kaplan-Meier分析表明在淋巴结阴性组,AR表达对预后分析无影响;在淋巴结受累组,AR阳性组5年生存率及中位生存时间均优于阴性组(89.3%比67.3%和56个月比37个月).将184例分为c-erbB2表达阴性及阳性两组,同样发现在c-erbB2表达阴性组,AR表达对预后无影响;在c-erbB2表达阳性组,AR阳性组5年生存率及中位生存时间均优于阴性组(80.0%比57.1%和57个月比37个月).结论 在预后相对较差的淋巴结受累及c-erbB2表达阳性的患者中,AR表达对进一步分析预后有一定价值,AR表达阳性者预后好于阴性病例.     

生长抑素受体和雌激素受体在原发性乳腺癌中的表达及其意义

目的研究生长抑素受体(SSTR)与雌激素受体(ER)、孕激素受体(PR)在原发性乳腺癌中的表达及其意义。方法 采用免疫组织化学链霉菌抗生物素蛋白-过氧化酶(SP)法检测SSTR和ER、PR在68例乳腺癌中的表达。结果 在68例乳腺癌中,SSTR阳性表达44例(64.70％),ER、PR阳性表达51例(75.70％),ER、PR和SSTR同时阳性表达阳性41例(60.29％)。ER、PR和SSTR两者表达呈正相关(r=0.651 6,P<0.05)。SSTR阳性患者复发率和死亡率低于SSTR阴性者(P<0.05);SSTR阳性且ER、PR阳性患者复发率和死亡率明显低于SSTR阴性ER、PR阴性患者(P<0.01)。病理分化低的有47例,SSTR阳性表达36例(P>0.05)。结论SSTR表达与ER、PR表达有明显相关性,有可能作为判断乳腺癌预后的指标。     

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。     

粘着斑蛋白、雄激素受体在前列腺癌中的表达及相关性研究

目的:检测粘着斑蛋白(VCL)和雄激素受体(AR)在良性前列腺增生(BPH)和前列腺癌(PCa)中的表达情况,并分析其与PCa不同临床分期、病理分级、PSA水平之间的相互关系。方法:采用免疫组化法检测18例BPH组织,38例PCa组织中VCL、AR的表达。并分析两者在BPH、PCa中的表达差异,在PCa不同临床分期、病理分级、初次PSA检测水平的表达差异,以及两者之间的相关性。结果:VCL在PCa中的表达较BPH组织增多,AR表达在BPH、PCa中无明显差异;VCL、AR在PCa组织中的表达与肿瘤临床分期、病理分级密切相关,与PSA值无明显关系;VCL、AR在PCa组织中的表达存在正相关。结论:VCL在BPH、PCa的表达具有差异性,可以作为前列腺良、恶性疾病鉴别诊断的一个潜在指标;AR、VCL随PCa进展表达逐步下降,两者存在正相关,两者结合可以成为PCa进展的诊断、预后评价指标。     

胃癌中雌激素和孕激素受体的表达及其临床意义

目的 :应用相应单克隆抗体探讨胃癌中雌激素受体 (ER)和孕激素受体 (PR)表达的临床意义。方法 :用ER、PR单克隆抗体对 86例胃癌标本进行免疫组化 (S -P法 )染色。结果 :①ER、PR在 86例胃癌中阳性表达率分别为 43 .0 %、3 7.2 % ,两者共同阳性 2 4例 (2 7.9% ) ;②ER、PR在胃癌Borrmann第 4型、胃低分化腺癌、粘液腺癌和有淋巴结转移组其阳性率显著高于其它各组 (P <0 .0 1)。而与患者年龄、性别无关 (P >0 .0 5 ) ;③ER、PR共同阳性 2 4例中 ,17例接受化疗加三苯氧胺治疗 ,7例单用化疗 ,随访 3年 ,两者生存率有明显差异 (P <0 .0 5 )。结论 :ER、PR阳性表达的胃癌是一种激素依赖性肿瘤 ,其预后较差 ,但对接受化疗加内分泌治疗有较好效果 ,可延长患者生存期。     

前列腺干细胞抗原在前列腺癌中的表达及其与雄激素受体、雌激素受体联合检测的意义

目的探讨前列腺干细胞抗原(PSCA)在前列腺癌(PCa)和良性前列腺增生(BPH)中的表达,及其与雄激素受体(AR)、雌激素受体(ER)联合检测的临床意义。方法应用免疫组化方法检测PSCA、AR和ER在50例PCa和30例BPH标本中的表达。结果 PSCA在PCa中高表达,在BPH中少量表达或不表达,PSCA表达的变化与PCa的Gleason评分具有明显相关性。AR在PCa中的表达与其分化程度无明显相关性,与PSCA无明显相关性。ER在BPH中表达阳性率为100%,且普遍强阳性,在PCa中表达的阳性率为12%,均与PSCA的表达呈负相关。结论 PSCA在前列腺细胞增殖、肿瘤形成的演进过程中发挥重要作用,联合检测PSCA和ER有助于PCa和BPH的诊断和治疗。     

乳癌p53与雌、孕激素受体的表达及临床意义

目的 探讨乳癌p53与雌、孕激素受体的表达及其临床意义。方法 应用免疫组化技术PAP法，测定200例乳癌的p53与雌、孕激素受体。结果 p53( )，雌激素受体（ER）（＋），孕激素受体（PR）（＋）分别为34.0%,63.0%和64.0%。ER（＋）及PR（＋）共96例，ER（－）及PR（－）共35例，ER和PR表达一致率为79.0%。显示上述三指标的阳性表达与病人腋淋巴结转移、病理组织类型无关，但与病人年龄、月经状况有关。结论 乳癌p53阳性预后差，ER及PR阳性比阴性的患者预后好，p53，ER和PR测定有助于指导乳癌的临床治疗和判断预后。     

应激激活蛋白激酶及其磷酸化在晚期前列腺癌表达

目的:探讨应激激活蛋白激酶(JNK)与磷酸化JNK(p-JNK)在晚期前列腺癌(PCa)和良性前列腺增生(BPH)中的表达及意义。方法:收集晚期PCa组织蜡块40例,BPH组织蜡块21例。免疫组化法检测组织中JNK和p-JNK蛋白表达,并分析其与晚期PCa和BPH的关系,及与晚期PCa患者病理特征的关系。结果:BPH组与PCa组JNK蛋白阳性表达率分别为42.86%、52.50%,无统计学差异(P0.05)。在未转移癌和转移癌、Gleason≤7和Gleason7、PSA≤20μg/L和PSA20μg/L、生存时间5年和生存时间≤5年PCa中的JNK蛋白阳性表达率分别为53.85%和51.85%、58.82%和47.82%、57.14%和51.52%、60.00%和45.00%,无统计学差异(P0.05)。p-JNK蛋白在BPH组与PCa组中的阳性表达率分别为33.33%、35.00%,无统计学差异(P0.05)。在未转移癌和转移癌、Gleason≤7和Gleason7、PSA≤20μg/L和PSA20μg/L PCa中的p-JNK蛋白阳性表达率分别为30.77%和37.03%、35.29%和34.78%、43.75%和10.93%,无统计学差异(P0.05)。生存时间5年组pJNK阳性率为50%,生存时间≤5年组p-JNK阳性率为20.00%,有统计学差异(P0.05)。结论:p-JNK高表达的PCa组生存时间长,并与PCa的预后相关。     

ER及PR表达对乳腺癌新辅助化疗疗效的影响

目的 研究雌激素受体(ER)及孕激素受体(PR)的表达对于乳腺癌新辅助化疗(neoadjuvantchemotherapy,NACT)疗效的影响.方法 采用免疫组化法检测52例乳腺癌组织中接受NACT前后的ER及PR的表达,分析ER、PR表达与NACT疗效的关系.结果 ER(-)患者NACT有效率为85.0%(17/20);ER(+)患者为56.3%(18/32),两组间差异有统计学意义(P<0.05);PR(-)患者NACT有效率为80%(21/25),PR(+)患者为51.6%(14/27),两组间差异有统计学意义(P<0.05).结论 ER(-)及PR(-)乳腺癌患者在NACT中的获益分别较ER(+)及PR(+)者明显.测定激素受体的表达状态,可预测乳腺癌患者对NACT是否有效,初步指导肿瘤个体化辅助化疗.     

Prostatic cancer/benign prostatic hypertrophy. Subcellular distribution of estradiol/androgen receptors

Six microsomal population of estradiol and androgen receptors have been characterized in human benign prostatic hypertrophy (BPH) and prostate cancer (PCa). Estradiol receptor (ER) and androgen receptors (AR) were extracted using 0.6 M KCL and determined by the dextran-coated charcoal method. ER and AR levels were smaller in BPH plasma membranes (PM) than in Pca cases. For functions 3, 4, 6, the ER values in PCa were 25-38% less with regard to BPH ER values. Whereas in PCa, AR values obtained in all fractions were higher when compared to BPH AR values. In benign prostatic hypertrophy and prostatic cancer, ER and AR levels were significantly higher in the nuclear fraction. In the nuclear fraction, ER and AR levels in BPH and PCa were significantly different. The subcellular distribution of AR and ER in BPH and PCa constitutes a reservation mechanism and processing a receptors for their continued growth.     

Steroid receptor profile and receptor stability in subfractions of human prostatic tissues

Summary Androgen (AR), progesterone (PR), and estrogen (ER) receptor contents in cytosol and salt-extractable nuclear subcompartments from 6 normal, 39 benign hyperplastic (BPH), and 7 malignant prostatic tissue specimens were analyzed by radioligand-binding assay techniques. In addition, the temperature stability of AR and PR was measured in another three BPH specimens. Five punch-needle biopsy samples from prostate cancers were also analyzed for AR and PR content. All receptor data were calculated from saturation analyses. The highest AR content was found in the cytosol and nucleic from malignant prostatic tissues. The highest PR concentrations were found in BPH cytosol, whereas nuclei of all types of tissues were negative with regard to this receptor. Markedly lower concentrations of ER were found in cytosol and nuclei from BPH as compared with malignant and normal tissues. PR was the most temperature-stable receptor; a marked receptor loss at room temperature was not registered until after 12 h. AR was stable for 4–5 h in cytosol and for 8–9 h in nuclei. Needle-biopsy specimens from prostate cancer showed highly variable and confusing results for AR and PR content, indicating that microassay studies using biochemical techniques on small tissue samples are unreliable and should not be recommended.     

Steroid receptors and hormone responsiveness of human prostatic carcinoma

Androgen (AR), estrogen (ER), and progesterone (PR) receptors have been found in human prostatic hyperplasia (BPH) and prostatic carcinoma (PC) (AR mainly in the epithelial compartment and ER in the stromal compartment). These steroid receptors have been studied in the cytosol of 59 prostatic cancers in order to select patients to be treated with endocrine therapy (orchiectomy, administration of antiandrogens). Tissues were collected through transvesical resection and needle biopsy. Tritiated metribolone (R1881), 17b-estradiol and promegestone (R5020) with the use of exchange assay and a dextran-coated charcoal method have been usually employed. In some specimens receptor content was also analyzed in the nuclear fraction. AR was found in the cytosol of 47 of 59 (79.66%), ER in 14 of 26 (53.85%), and PR in 13 of 15 (86.67%) tumors examined. AR was detected in the nuclear fraction of 11 of 26, ER in nine of 13, and PR in two of four tumors examined. AR was found to correlate with the histological grade of the cancers, whereas no correlation could be demonstrated between the histological grade and cytoplasmic or nuclear ER. On the basis of receptor studies, hormonal treatment was started with orchiectomy followed by the administration of cyproterone acetate (CPA) 50 mg twice a day in 26 eligible out of 38 patients available for follow-up with tumors examined for cytoplasmic AR. The response to hormonal therapy depended strictly on the presence of AR. The endocrine treatment used seems, in our opinion, to be the most advisable form of therapy, and is capable of blocking the uptake of androgens of extratesticular origin by prostatic cells. Although the clinical advantages of progestational therapy for human PC are not yet established, the presence of PR in prostatic carcinoma leads us to believe that progestational compounds as well as the progestational activity of CPA may be effective on tumor growth of tissues that are positive for PR.     

Sex steroid receptors in normal and hyperplastic human prostate

The concentrations of sex steroid receptors (per unit DNA) were measured in normal periurethral and peripheral prostatic tissue samples from seven men (mean age 64 years; range 54-71 years) undergoing cystectomy for bladder cancer, and in hyperplastic nodules from 15 men with BPH (mean age 69 years; range 60-89). Occupied androgen (AR) and estrogen (ER) receptors were measured with an improved exchange procedure, where receptor-binding sites were stabilized by a combinatorial procedure involving careful washout of extracellular secretory products (including proteases) prior to homogenization, inclusion of 0.5 mM phenylmethyl sulfonylfluoride (PMSF) and 20 mM molybdate in the exchange medium, and long-term incubation at 0-4 degrees C. Bound radioligands were separated by a hydroxylapatite (HAP) batch adsorption procedure. Maximal specific exchange binding of 3H-R 1881 or 3H-estradiol in total homogenates of human prostate samples was achieved after incubation periods of about 72 h at 0-4 degrees C. In contrast, progestin receptors (PR) were readily available for binding 3H-R 5020; thus overnight binding at 0-4 degrees C was routinely used to measure PR. Binding specificities and equilibrium binding constants (calculated from 8-point Scatchard plots, correcting for nonsaturable binding) were found to be characteristic for AR, PR, and ER, respectively. The receptor results obtained in this study demonstrate that no significant differences existed in total AR per unit DNA between hyperplastic and either central or peripheral prostatic tissue samples; PR was present in both zones of normal prostatic tissue as often as in BPH samples, with PR concentrations significantly lower in hyperplastic samples; and ER was irregularly detected in both normal and hyperplastic tissue in low concentration relative to AR and PR; the frequency of ER detection was much lower in BPH than in normal prostate tissue. Studies of steroid receptor content relative to enzyme markers specific for epithelial and stromal cells in BPH samples showed a positive correlation between acid phosphatase activity (a specific marker for epithelial cells) and both AR and PR. No correlation was observed between AR or PR with either prolyl hydroxylase or myosin ATPase (specific markers for stromal cells). These observations suggest that PR, as well as AR, is primarily associated with the epithelial elements of prostate. Because of the relative infrequency of ER, similar correlation of ER with enzyme markers was not possible.     

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。     

前列腺带性结构及其雄激素、雌激素、表皮生长因子受体分布特征的研究

为了探讨雄激素受体（ＡＲ）、雌激素受体（ＥＲ）、孕激素受体（ＰＲ）和表皮生长因子受体（ＥＧＦＲ）在前列腺带性结构中的分布，应用单饱和剂量测定法，分别测定了前列腺移行带、外周带组织中ＡＲ、ＥＲ、ＰＲ和ＥＧＦＲ的含量。结果表明，在１１例前列腺增生症（ＢＰＨ）患者２２份标本中，移行带和周围带ＡＲ全部阳性；尽管ＡＲ浓度个体差异很大，但是两带之间仍有密切相关性（Ｐ＜０００１）；周围带ＡＲ浓度高于移行带，两带ＡＲ浓度均高于ＰＲ、ＥＲ；ＰＲ和ＥＲ在前列腺带性结构上没有明显差异。ＥＧＦＲ在移行带明显高于周围带。研究证实了ＡＲ、ＥＲ、ＰＲ，ＥＧＦＲ在前列腺移行带和周围带上的分布特征。     

Breast hormonal receptors test should be repeated on excisional biopsy after negative core needle biopsy

Therapeutic decision-making for women diagnosed with breast cancer requires accurate determination of the estrogen receptor (ER) and progesterone receptor (PR). Decisions about adjuvant therapy are often based on the immunohistochemical (IHC) profile of the core needle biopsy sample (CNB) because the staining is not repeated on the final excisional biopsy (EB). The purpose of this study was to assess the concordance of breast cancer IHC receptor assays on CNB and EB. We identified 176 patients with matching breast CNB and EB that had available ER and PR. While the CNBs were processed and stained in different laboratories, the EB were processed and stained in our institution. The following antibodies were used 1D5, 6F11 and SP1 for ER, and PgR636, 16 and 1E2 for PR, from Dako, Leica and Ventana respectively. Correlation of scores of CNBs with matching EB was analyzed using Spearman correlation coefficients. Sensitivity, specificity, overall agreement and the kappa statistic were used to measure the concordance between CNB and EB. For CNB, there were 141 (80.1%) cases positive for ER and 118 (67%) cases positive for PR. For EB, there were 143 (81.3%) cases positive for ER and 130 (73.9%) cases positive for PR. Overall agreement for ER and PR was seen in 93% (95% CI = 0.88, 0.96) and 90% (95% CI = 0.84, 0.94) respectively. Overall, ER- CNB/ER+ EB was seen in seven (4%) cases and PR- CNB/PR+ EB in 15 (8.5%) cases. ER+ CNB/ER- EB was seen in five (2.8%) cases and PR+ CNB/PR- EB in three (1.7%) cases. To avoid erroneous omission of life-saving endocrine therapy ER and PR should be repeated on the EB for patients whose CNB has negative hormonal receptors.     

LC3A蛋白在前列腺癌中的表达及意义

目的:探讨LC3A蛋白在前列腺癌中的表达及意义。方法:应用免疫组化方法检测LC3A在54例前列腺癌和14例良性前列腺增生(BPH)中的表达状况。结果:LC3A蛋白阳性信号定位于细胞质和/或细胞核,在前列腺癌中胞质强阳性率为90.7%,在BPH中的胞质强阳性率为14.3%,两组差异有显著性(P0.01);并发现前列腺癌中22例核着色(40.7%),LC3A胞质表达与细胞核表达无相关性(P0.05)。LC3A表达与Gleason评分呈正相关(胞质r=0.297,P=0.029;胞核r=0.288,P=0.034)。LC3A与患者的临床分期、年龄、雄激素受体(AR)及术前患者血清PSA及结合PSA(cPSA)水平均无相关性(P0.05)。LC3A在前列腺癌及BPH组织间质中的纤维细胞及平滑肌细胞也见着色。AR在前列腺癌中阳性率为74.1%(40/54),在BPH的阳性率为64.3%(9/14)。两者阳性率差异无统计学意义。结论:LC3A可能与前列腺癌的发生、分化及预后有关。     

雄激素受体CAG重复多态性与BPH和PCa相关性的meta分析

目的:通过meta分析探讨雄激素受体(AR)基因CAG重复多态性与良性前列腺增生(BPH)和前列腺癌(PCa)发病风险的关系。方法:检索国内外大型数据库发表的AR基因CAG重复多态性与BPH和PCa相关性的文献,基于异质性检验的结果,分别采用M-H固定效应模型和随机效应模型合并比值比(OR)效应量,采用Begg和Egger偏倚分析评估本项meta分析的发表偏倚,系统评价AR基因CAG重复多态性与BPH和PCa发病风险的关系,并按种族进行分层分析。结果:检索获得文献29篇,最终纳入4篇符合条件的文献,累计BPH患者485例、PCa患者767例、正常对照组709例。BPH组和正常对照组间不存在异质性,M-H固定效应模型合并效应量后提示低CAG重复多态性与BPH无相关性。PCa组和BPH组及对照组间均存在异质性,随机效应模型提示低CAG重复多态性与PCa的风险呈正相关(OR PCa/对照=1.45,OR PCa/BPH=1.86,OR PCa/(BPH+对照)=1.66)。种族分层的亚组分析提示,低CAG重复多态性与PCa发病风险在种族间存在差异。Begg和Egger偏倚分析显示各组比较中均无显著发表偏倚。结论:AR受体低CAG重复多态性与PCa发病风险呈正相关,与BPH发病风险无相关性。