子宫内膜样腺癌组织中内分泌细胞及其雌、孕激素受体的研究

目的　探讨子宫内膜样腺癌组织中内分泌细胞与雌、孕激素受体的关系。方法　采用免疫组化S -P法 ,检测 5 0例子宫内膜样腺癌组织中嗜铬素A(CgA )、雌激素受体 (ER )及孕激素受体 (PR )的表达情况 ,并对CgA阳性的子宫内膜样腺癌组织分别进行CgA /ER及CgA/PR双重免疫组化染色。 结果　子宫内膜样腺癌组织中CgA阳性率为 44 .0 % (2 2 /5 0 )。ER阳性率为2 8.0 % (14 /5 0 ) ,PR阳性率为 5 0 .0 % (2 5 /5 0 )。子宫内膜样腺癌CgA阳性组与阴性组之间ER表达率无显著性差异 (P >0 .0 5 ) ,但PR表达率有显著性差异 (P <0 .0 5 )。 2 2例CgA阳性子宫内膜癌细胞中CgA /ER同时表达率为 10 .1% (2 2 1/2 2 0 8个细胞 ) ,CgA/PR同时表达率为 2 0 .1% (4 90 /2 44 0个细胞 )。结论　子宫内膜癌组织出现较多的内分泌细胞及ER、PR的缺失是肿瘤异质性的表现。内分泌细胞不仅影响肿瘤细胞的生长 ,而且可能与子宫内膜癌对激素治疗的抗性或激素治疗后的复发有关     

雌孕激素及米非司酮对人子宫内膜癌细胞孕激素受体亚型调控的研究

目的:通过体外实验探讨雌激素、孕激素及米非司酮对人子宫内膜癌细胞孕激素受体亚型表达的调节。方法:体外培养表达不同孕激素受体亚型的人子宫内膜癌细胞HECCA-A(PRA+)、HECCA-B(PRB+)及HECCA-AB(PRA+和PRB+),分别加入雌激素、孕激素和米非司酮,作用24、48h后采用蛋白质印迹法测定各组细胞中2种孕激素受体亚型蛋白的表达。结果:雌激素作用48 h后,HECCA-A、HECCA-AB细胞的PRA表达水平明显升高,PRA/PRB比值升高,P<0.05;孕激素及米非司酮作用48 h后,HECCA-B、HECCA-AB细胞的PRB表达水平明显降低,PRA/PRB比值升高,P<0.05。结论:雌激素上调子宫内膜癌细胞PRA的蛋白表达水平,孕激素及米非司酮下调PRB的蛋白表达水平。     

端粒酶hTERT在子宫内膜癌中的表达及意义探讨

 目的　探讨端粒酶hTERT基因蛋白表达与子宫内膜癌发生发展的关系及对内膜癌诊断、预后的临床意义。方法　采用免疫组化方法对 33例子宫内膜癌、36例绝经期子宫内膜及 36例子宫内膜增生过长标本进行端粒酶hTERT、雌激素受体ER及孕激素受体PR检测 ,同时与正常增殖期 ,分泌期子宫内膜进行对照。结果　hTERT在子宫内膜癌中的表达强度明显高于其他内膜病变 ,有显著性差异 (P<0 .0 5 ) ;hTERT在子宫内膜癌中的表达与肌层浸润及临床分期呈正相关 ;与病理分级及雌、孕激素受体ER ,PR呈负相关。结论　上述结果提示端粒酶hTERT在子宫内膜癌的发生发展中可能起重要作用 ,端粒酶hTERT与ER ,PR的联合检测可能成为子宫内膜癌判断预后的一个指标。     

雌、孕激素受体与子宫内膜癌相关性的研究

目的　通过对雌、孕激素受体表达水平的检测分析 ,探讨雌、孕激素受体的表达水平与子宫内膜癌的发生、发展的关系。方法　收集我科经手术治疗的新鲜活体组织标本 ,并经病理组织学确诊的子宫内膜癌 30例。采用较新的LSAB免疫组织化学方法检测雌激素受体 (ER)和孕激素受体 (PR)的表达水平。结果　ER和PR的阳性率一致 ,均为 6 6 6 7% :组织学分级高分化腺癌 (Ⅰ级 )的阳性率为 4 0 % ,明显高于中、低分化者 (Ⅱ、Ⅲ级 ) ;临床分期早期 (Ⅰ期 )的阳性率为 4 3 33% ,明显高于中、晚期 (Ⅱ、Ⅲ期 )患者 (P <0 0 1)。在同一标本不同部位的癌灶、癌旁和正常组织中ER和PR的阳性率显示癌灶组织明显低于癌旁和正常组织(P <0 0 5 )。结论　ER和PR的表达水平与子宫内膜癌的组织学分级和临床分期有一定的关系 ,高分化癌的ER和PR表达水平高 ,低分化癌的ER和PR含量低 ;临床分期早期患者的ER和PR含量高 ,中、晚期患者的ER和PR含量低。笔者认为 :ER和PR的检测对子宫内膜癌的组织学分化趋势、分级及临床分期和内分泌治疗与对预后的监测有指导意义     

米非司酮抑制子宫内膜癌细胞体外增殖的作用

 目的 观察抗孕激素米非司酮对人子宫内膜癌细胞体外增殖活性的影响，并探讨其作用机制。方法 体外培养子宫内膜癌HHUA细胞株，不同浓度米非司酮处理细胞24-96h，应用四甲基偶氮唑蓝（MTT）比色法观察米非司酮对HHUA细胞增殖活性的影响；免疫组化技术观察HHUA细胞Ki-67和c-myc基因表达的变化。结果 米非司酮以时间一剂量依赖性方式，显著地抑制人子宫内膜癌HHUA细胞的体外增殖活性（P〈0．05）；当米非司酮浓度≥5μmol／L作用细胞24h后，子宫内膜癌HHUA细胞Ki-67和c-myc基因表达水平明显降低。结论 抗孕激素米非司酮以时间一剂量依赖性方式显著抑制子宫内膜癌HHUA细胞的体外增殖活性，并与降调Ki-67和c-myc基因表达密切相关。     

子宫内膜癌雌、孕激素受体和C-erbB-2检测的临床意义

目的 检测子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)及癌基因蛋白C-erbB-2表达的阳性率并探讨其与预后的关系.方法 用免疫组织化学法对32份子宫内膜癌标本进行了ER、PR及C-erbB-2的检测.结果 子宫内膜癌组织中ER、PR、C-erbB-2的阳性率分别为53.1%、50.0%、46.9%.ER、PR的阳性表达率与癌组织的细胞分化程度有关,随着子宫内膜癌组织学分级的增高,ER、PR阳性表达率逐渐降低,C-erbB-2的阳性表达率与肿瘤病理分级呈正相关,与ER、PR表达呈负相关.结论 ER、PR、C-erbB-2均反映了子宫内膜癌的生物学行为,其测定对预测预后、指导选择内分泌治疗具有重要意义.     

p27~(kipl)蛋白与雌、孕激素受体在子宫内膜组织中的表达及其意义

目的　探讨 p2 7kipl、雌激素受体 (ER)与孕激素受体 (PR)在子宫内膜癌中的表达及意义。方法　用免疫组化法检测 6 6例子宫内膜癌、2 9例子宫内膜非典型增生病变和 31例正常子宫内膜组织中p2 7kipl蛋白及其癌组织中ER和PR的表达。结果　在癌组织中p2 7kipl的表达率为 5 3.0 % ,明显低于非典型增生病变的 75 .8%和正常子宫内膜的 87.1% ,并与其分级有关 ;ER和PR的表达与p2 7kipl相似。结论　p2 7kipl与此癌的发展和恶性程度有关 ,这对其治疗和预后有参考价值。     

米非司酮对子宫内膜癌裸鼠移植瘤细胞凋亡调控的研究

目的探讨抗孕激素米非司酮对人子宫内膜癌HHUA细胞裸鼠移植瘤细胞凋亡的调控作用。方法体外培养人子宫内膜癌HHUA细胞,裸鼠皮下接种HHUA细胞建立裸鼠移植瘤动物模型,随机分为2组,分别应用米非司酮、精制花生油治疗4周,应用流式细胞术(FCM)检测各组裸鼠移植瘤细胞周期时相和凋亡率;免疫组化技术检测凋亡基因bcl2、Fas和FasL蛋白的表达情况。结果米非司酮治疗组裸鼠移植瘤细胞G0/G1期比例升高,S期细胞比例(SPF)降低(P<0.05),移植瘤细胞凋亡率为15.03%±2.19%,明显高于对照组(3.06%±1.13%)(P<0.01);移植瘤细胞bcl2蛋白表达水平明显下降,而Fas蛋白表达水平升高,与对照组比较,均有显著性差异(P<0.05)。结论抗孕激素米非司酮通过调节移植瘤细胞周期分布和凋亡基因,抑制肿瘤细胞增殖,诱导细胞凋亡。     

甾体激素受体PR、ER表达与子宫内膜癌淋巴结转移关系的研究

目的 :探讨激素受体PR、ER表达与子宫内膜癌淋巴结转移的关系。方法 :采用免疫组化法对15 9例子宫内膜组织中的PR、ER表达进行检测。结果 :PR阴性子宫内膜癌的淋巴结阳性率明显高于PR阳性者 ,两者差异有显著性 (P <0 0 1) ;ER阳性和阴性的淋巴结阳性率差异无显著性 (P >0 0 5 ) ;PR、ER阴性表达的淋巴结阳性率为 5 1 5 % ,而PR、ER阳性者为 10 7% ,两者差异有极显著性 (P <0 0 1)。结论 :PR表达与子宫内膜癌的淋巴结转移更具相关性 ,可将PR、ER表达结果作为评估盆腔淋巴结转移的参考指标之一     

p27 kipl蛋白与雌、孕激素受体在子宫内膜组织中的表达及其意义

 目的　探讨 p2 7kipl、雌激素受体 (ER)与孕激素受体 (PR)在子宫内膜癌中的表达及意义。方法　用免疫组化法检测 6 6例子宫内膜癌、2 9例子宫内膜非典型增生病变和 31例正常子宫内膜组织中p2 7kipl蛋白及其癌组织中ER和PR的表达。结果　在癌组织中p2 7kipl的表达率为 5 3.0 % ,明显低于非典型增生病变的 75 .8%和正常子宫内膜的 87.1% ,并与其分级有关 ;ER和PR的表达与p2 7kipl相似。结论　p2 7kipl与此癌的发展和恶性程度有关 ,这对其治疗和预后有参考价值。     

Oestrogen receptor negative-progesterone receptor positive phenotype in 1,211 breast tumours.

From 1,211 breast cancers, 15 oestrogen receptor (ER) negative-progesterone receptor (PgR) positive breast cancers by conventional dextran coated charcoal steroid binding assays in cytosol were reassessed using Elisa techniques with monoclonal antireceptors antibodies in the cytosolic and nuclear fractions, and immunocytochemistry on cryostat sections. Three categories of results were found in this series. Two tumours were false negative ER due to receptor sites occupancy by hormonal contraceptive treatment. A second group of ten tumours, with high PgR concentrations and immunoreactive ER, corresponds to non ER-binding forms of receptors. One PgR positive tumour was found to be devoid of PgR by using monoclonal antiPgR antibodies might contain a progesterone binding cyst protein. Only two tumours were found to be true ER negative-PgR positive by all methods. This rare phenotype deserves further study of the regulation of the PgR gene.     

激素受体ER与PR及AR在男性乳腺癌与良性病变组织中的表达

目的:探讨激素受体(ER、PR和AR)在男性乳腺癌的表达及三种受体之间表达的相关关系。方法:采用免疫组化方法对ER、PR、AR三种受体进行检测,并用SPSS软件分析各组差异。结果:ER、PR在23例男性乳腺癌患者组织中表达阳性率较良性病变低,分别为82.6%、56.5%与良性疾病相比有明显的统计学差异(OR分别为:4.32和5.25,P<0.05),AR表达与ER、PR之间表达不相关。结论:男性乳腺癌患者中ER、PR表达阳性率较良性病变低,AR表达与ER、PR之间表达不相关。     

Transferrin receptor is inversely correlated with estrogen receptor in breast cancer

Summary The transferrin receptor (TfR) has been identified as a marker for proliferation in cells in culture and can be accurately quantitated by specific radioimmunoassay. This study directly quantifies levels of TfR and compares them to levels of estrogen receptor (ER) and progesterone receptor (PgR) in biopsy material obtained from patients with infiltrating ductal carcinoma of the breast. A comparison of ER and TfR levels displayed an exponential distribution which was log-normalized to yield a linear inverse relationship (r = –.44). Although ER was strongly correlated with PgR, there was no correlation pattern between TfR and PgR. Multiple regression analysis indicated that 73% of ER levels could be predicted by a combination of the other two markers, PgR (representing degree of differentiation) and TfR (representing growth rate). Transferrin receptor levels were also found to be correlated (p<.05) with menopausal status, with tumors from premenopausal patients exhibiting higher levels, whereas the opposite pattern was shown for estrogen receptor levels (p<.02). Neither steroid receptor nor transferrin receptor levels were correlated to stage of disease or presence of nodal involvement. Addition of TfR level as an independent marker for proliferation may facilitate the decision-making process in the treatment of individual cases of carcinoma of the breast.     

Androgen receptor in estrogen receptor positive breast cancer: Beyond expression

In recent years, new therapeutic approaches have reshaped the overall strategy of breast cancer (BC) treatment and have markedly improved patient survival. This is, in part, due to novel therapies for estrogen receptor (ER)-positive BC. Unfortunately, many patients present de novo resistance to these therapies or develop an acquired resistance over time. Therefore, research is now focused on discovering new molecular targets to overcome these resistances. Interestingly, preclinical and clinical studies have shown a critical role for the cross-talk between androgen receptor (AR) and ER in luminal-like BC. AR is expressed in >60% of BC and in up to 90% of ERα-positive tumors. Multiple studies suggest that AR is associated with a favorable prognosis. However, AR overexpression and, in particular, the high AR:ER ratio, seem to be involved in resistance to hormonal treatment. In this setting, a group of BCs could benefit from AR-inhibitors; nevertheless, some ER-positive BC patients do not seem to benefit from this strategy. Therefore, it is crucial to identify biomarkers that would enable the selection of patients who might benefit from combination treatment with ER and AR inhibitors.     

MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer

Introduction

Breast cancer is a heterogeneous disease encompassing a number of phenotypically diverse tumours. Expression levels of the oestrogen, progesterone and HER2/neu receptors which characterize clinically distinct breast tumours have been shown to change during disease progression and in response to systemic therapies. Mi(cro)RNAs play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as regulators of tumour behaviour and progression. The aims of this study were to identify miRNA signatures that accurately predict the oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancer phenotypes and progression.

Methods

Expression profiling of 453 miRNAs was performed in 29 early-stage breast cancer specimens. miRNA signatures associated with ER, PR and HER2/neu status were generated using artificial neural networks (ANN), and expression of specific miRNAs was validated using RQ-PCR.

Results

Stepwise ANN analysis identified predictive miRNA signatures corresponding with oestrogen (miR-342, miR-299, miR-217, miR-190, miR-135b, miR-218), progesterone (miR-520g, miR-377, miR-527-518a, miR-520f-520c) and HER2/neu (miR-520d, miR-181c, miR-302c, miR-376b, miR-30e) receptor status. MiR-342 and miR-520g expression was further analysed in 95 breast tumours. MiR-342 expression was highest in ER and HER2/neu-positive luminal B tumours and lowest in triple-negative tumours. MiR-520g expression was elevated in ER and PR-negative tumours.

Conclusions

This study demonstrates that ANN analysis reliably identifies biologically relevant miRNAs associated with specific breast cancer phenotypes. The association of specific miRNAs with ER, PR and HER2/neu status indicates a role for these miRNAs in disease classification of breast cancer. Decreased expression of miR-342 in the therapeutically challenging triple-negative breast tumours, increased miR-342 expression in the luminal B tumours, and downregulated miR-520g in ER and PR-positive tumours indicates that not only is dysregulated miRNA expression a marker for poorer prognosis breast cancer, but that it could also present an attractive target for therapeutic intervention.     

雌激素受体及孕激素受体在肝内及肝外胆管癌中的表达

 目的　对比研究雌激素受体（ER）、孕激素受体（PR）在肝内、外胆管癌中的表达情况。方法　应用免疫组织化学法,检测24例肝内胆管癌和34例肝外胆管癌组织中ER和PR的表达水平。结果　在肝内胆管癌中,ER和PR的阳性表达率分别为29 %（7／24）和46 %（11／24）,组织学分级高分化组的9例中3例ER阳性表达,中分化组的11例中3例阳性表达,低分化组的4例中1例阳性表达;不同分级中,PR阳性表达分别为2、7、2例,各组织学分级间ER和PR的表达差异无统计学意义（均P＞0.05）。ER和PR在34例肝外胆管癌中均呈阴性表达。结论　ER和PR在肝内、外胆管癌中的表达水平明显不同,仅表达于肝内胆管癌,可能参与了肝内胆管癌的发生过程。     

Progesterone receptor expression in neurofibromas

Neurofibromas are benign tumors of the peripheral nerve sheath, which occur sporadically and in association with the common familial cancer syndrome, neurofibromatosis type 1. There are intriguing links between the growth of neurofibromas and levels of circulating hormones: neurofibromas often first appear around the time of puberty, increase in number and size during pregnancy, and shrink after giving birth. We examined 59 human neurofibromas for the expression of estrogen and progesterone receptors (PRs), because their ligands, estrogen and progesterone, were attractive candidate hormones. The majority (75%) of neurofibromas expressed PR, whereas only a minority (5%) of neurofibromas expressed estrogen receptor. Within neurofibromas, PR was expressed by non-neoplastic tumor-associated cells and not by neoplastic Schwann cells. We hypothesize that progesterone may play an important role in neurofibroma growth and suggest that antiprogestins may be useful in the treatment of this tumor.     

Estrogen receptor in malignant melanoma

The significance of an estrogen binding protein (ER) in malignant melanoma remains controversial. We have prospectively assayed for ER on 141 patients with malignant melanoma and correlated the presence of the ER with known prognostic variables. The overall incidence of ER was 43%. The incidence of ER in males was 38.7% and 50% in females (not significant). There is an increased incidence of ER+ melanoma in women with extremity lesions (P = .08). The disease-free interval (DFI), survival, and recurrent interval were 42.0 +/- 4.0, 52.3 +/- 4.3, 13.7 +/- 1.7 months in ER- patients; 63.7 +/- 11.6, 76.1 +/- 11.4, 26.5 +/- 7.3 months in ER+ patients (1 to 10 fmol/mg cytosol protein), and 69.8 +/- 17.9, 102.7 +/- 27.9, 29.4 +/- 9.9 months in ER+ patients (greater than 10 fmol/mg cytosol); respectively. When ER+ groups were combined, the DFI in women with ER+ lesions was significantly longer than those with ER- tumors (P less than .05). Cox multivariate analysis demonstrated that ER status is a significant variable of survival along with thickness level and nodal status. These observations suggest that ER may be a marker for a more biologically indolent melanoma.     

Estrogen receptor and progesterone receptor are prognostic factors in soft tissue sarcomas

Estrogen (ER) and progesterone receptor (PgR) regulate growth and cell differentiation upon ligand-dependent and ligand-independent activation. In breast cancer and gynecological tumors their expression are known predictors of endocrine therapy benefits and a favourable therapy-independent prognosis. In soft tissue sarcomas, their expression profile is poorly defined and their significance is uncertain. We investigated the prognostic impact of ER and PgR in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STSs). Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays (TMAs) were constructed for each specimen. Immunohistochemistry (IHC) was used to evaluate marker expression in tumor cells. In univariate analyses, the expression of neither ER nor PgR (P=0.333 and 0.067, respectively) were significant prognosticators in the total cohort. However, measured separately for each gender, ER positivity was a significant favourable indicator for disease specific survival (DSS) in women (P=0.017) while PgR positivity had inverse impact in men (P=0.001). Among the four possible coexpression profiles, ER-/PgR+ was significantly least favourable for survival in the univariate analysis (P<0.001). In the multivariate analysis, the ER-/PgR+ phenotype was an independent negative prognostic factor for DSS (HR=1.9, 95% CI=1.2-3.1, P=0.008) in addition to patient's nationality, tumor depth, histological entity, malignancy grade, metastasis at diagnosis, surgery and positive resection margins. The present findings indicate that ER and PgR have significant gender dependent impact on DSS in non-GIST STSs.