正常,增生过长子宫内膜及内膜癌ER,PR检测探讨

本实验用亲和组化法检测增生期、分泌期、增生过长子宫内膜及内膜癌的雌激素受体(estrogen receptor,ER)和孕激素受体(Progesterone receptor,PR)。各组强阳性率结果:增生期内膜ER为56.5%,PR为43.5%;分泌期内膜ER仅为6.5%,PR为3.5%;增生过长内膜ER为25%;子宫内膜癌ER为13%,且与分化程度呈正比。统计学处理,增生期子宮内膜与分泌期、增生过长内膜及內膜癌的受体水平均差异有显著性,P<0.01、P<0.05。增生过长子宫内膜与内膜癌受体水平及分布特点差异无显著性,P>0.05。癌周残留内膜间质细胞及肌层组织均显示相当水平的ER、PR。本文就ER、PR在子宫内膜癌的发生、临床、病理的关系及检测方法进行了讨论。     

消化道癌性激素受体的免疫组化研究

本文对129例消化道癌的ER、PR、AR进行了免疫组化检测。结果发现:食管癌、胃癌、大肠癌的ER、PR、AR及鳞癌与腺癌的3种性激素受体阳性率,均无显著性差异。贲门胃底癌的3种性激素受体阳性率分别高于胃体和胃窦癌,其中ER和AR阳性率有显著性差异(P<0.01,P<0.05)。3种消化道癌的ER、PR、AR阳性率与性别、病理类型、生长方式、分化程度、浸润深度、局部淋巴结转移及临床分期亦均无统计学显著性。     

人眼睑板腺和Zeis腺性激素受体定性定位的免疫组织化学研究

目的探讨性激素受体在睑板腺和Zeis腺的定性和定位分布。方法采用免疫组织化学技术和DAB显色方法显示雌激素受体（ER）、孕激素受体（PR）、雄激素受体（AR）在睑板腺和Zeis腺上皮的表达。结果胎儿4个月睑板腺和Zeis腺上皮呈ER、PR、AR阳性;而儿童至成人组睑板腺和Zeis腺上皮呈ER、AR阳性。各种性激素受体定位同时出现在细胞膜、细胞质和细胞核。ER在睑板腺和Zeis腺上皮阳性表达率在年龄组间比较,均无显著性差异（P〉0．05）;PR在睑板腺和Zeis腺上皮阳性表达率在年龄组间比较,均有显著性差异（P〈0．05）：AR在睑板腺上皮阳性表达率在年龄组间比较无显著性差异（P〉0．05）,而Zeis腺上皮阳性表达率则有显著性差异（P〈0．05）。ER、PR、AR阳性表达率在胎儿组性别间比较和ER、AR阳性表达率在儿童至成人组性别间比较均无显著性差异（P〉0．05）。结论胎儿4个月睑板腺和Zeis腺上皮ER、PR、AR即有表达。出生后睑板腺和Zeis腺上皮仅存在ER和AR,以ER为主。ER、PR、AR定位在细胞膜、细胞质和细胞核。     

乳腺癌复发转移灶与原发灶中ER、PR、HER-2、p53、Ki-67的表达差异

目的 探讨ER、PR、HER-2、p53、Ki-67在乳腺癌复发转移灶与原发灶中的表达差异。方法 采用免疫组化En Vision两步法检测156例乳腺癌原发病灶及对应的复发或转移灶中ER、PR、HER-2、p53及Ki-67的表达,比较各指标的表达差异,并分析发生局部复发或远处转移的乳腺癌临床病理特征及与原发癌相比与各指标表达的一致性。结果 乳腺癌局部复发组和远处转移组与肿瘤分期(P=0.015)、肿瘤直径(P=0.005)差异有显著性;与患者年龄、组织学分级和腋窝淋巴结状态的差异无显著性(P0.05)。复发转移灶ER、PR阳性率比原发灶均有所下降,但差异无显著性;ER、PR表达不一致(分别为18.6%、19.2%),差异有显著性(P=0.024,P=0.043);原发灶与复发转移灶HER-2表达有较高的一致性,表达不一致占5.1%;原发灶与复发转移灶p53的阳性率差异不大,p53表达不一致占14.1%;复发转移灶Ki-67高表达者比原发灶多,Ki-67表达不一致占30.8%,差异有显著性(P0.001)。局部复发组和远处转移组各指标表达不一致的差异无显著性。结论 乳腺癌原发灶与复发转移灶ER、PR和Ki-67表达存在不一致性,HER-2表达有较高一致性。因此,检测乳腺癌复发转移灶中各指标表达对治疗方案选择和预后有重要意义。     

ER、PR及其相应拮抗剂与甲状腺癌的相关性研究进展

雌激素受体(ER)、孕激素受体(PR)在甲状腺癌中的异常表达说明性激素受体在甲状腺癌的发病机制中起重要作用.ER、PR通过经典的基因途径及非基因途径对甲状腺癌的发生、发展及生物学特征产生重要影响.性激素受体拮抗剂抑制甲状腺癌细胞增殖作用的研究,将为甲状腺癌的治疗提供新的选择方案.     

子宫内膜异位症模型大鼠子宫内膜雌、孕激素受体表达的变化

利用大鼠子宫内膜异位症 (内异症 )动物模型 ,采用逆转录聚合酶链反应 (RT PCR)技术 ,检测子宫内膜雌激素受体 (ER)和孕激素受体 (PR)mRNAs的表达 ,探讨内异症的发病机理及激素治疗的可能性。结果表明 ,内异症模型组大鼠异位内膜ER、PRmRNAs的表达低于在位内膜及对照组正常子宫内膜 ,与后两者比较差异有显著性意义(P <0 0 1 ) ;而模型组在位内膜ER、PRmRNAs的表达与正常对照组比较差异无显著性意义。内异症模型组异位内膜ER PRmRNA比值大于在位内膜及正常子宫内膜ER PRmRNA比值 (P <0 0 1 )。提示内异症大鼠异位内膜ERmRNA表达的降低在内异症的发生与发展中起着一定的作用     

男性乳腺癌组织中p57~(kip2)、ER、PR的表达及其意义

目的 探讨p57~(kip2)、ER、PR在男性乳腺癌(male breast cancer,MBC)中的表达及意义。方法 采用免疫组化Eli Vision法检测50例MBC、20例男性乳腺导管内原位癌(ductal carcinoma in situ,DCIS)和20例男性乳腺发育(gynecomastia,GYM)组织中p57~(kip2)、ER、PR蛋白的表达。结果 p57~(kip2)蛋白在GYM中的表达最高,在MBC中的表达最低;MBC与DCIS、GYM中的表达相比,差异有显著性(P0.05);p57~(kip2)蛋白表达在DCIS与GYM中相比,差异有显著性(P0.05)。ER、PR蛋白在GYM中的表达最高,在MBC中的表达最低;ER、PR蛋白表达在MBC与GYM中相比,差异有显著性(P0.05)。在MBC中,三者表达均与临床分期、组织学分级有关(P0.05),p57~(kip2)蛋白表达与淋巴结转移有关(P0.05);p57~(kip2)与ER呈负相关(P0.05),p57~(kip2)与PR、ER与PR均呈正相关(P0.05)。结论 男性乳腺组织从良性增生到恶性转化中p57~(kip2)、ER、PR蛋白表达逐渐降低,甚至完全丧失;联合检测p57~(kip2)、ER、PR有助于MBC的诊断及预后判断。     

性激素结合球蛋白在乳腺癌中的表达及意义

目的 探讨性激素结合球蛋白(sex hormone-binding globulin,SHBG)在乳腺癌中的表达及意义.方法 采用免疫组化EnVision法检测SHBG、AR、ER在83乳腺癌中的表达,每例标本中均包括浸润性乳腺癌(invasive breast carcinoma,IBC)和原位癌(carcinoma in situ,CIS)组织.结果 CIS及IBC中SHBG表达与AR、ER无相关性,CIS中SHBG阳性68例(81.9%),IBC中阳性53例(61.9%),两者差异有显著性(P=0.007),AR、ER阳性乳腺癌中表达SHBG者临床分期低,差异有显著性(P值分别为0.049和0.013),SHBG阳性的乳腺癌中AR、ER均阳性者组织学分级低,差异有显著性(P=0.000).结论 AR、ER阳性乳腺癌中SHBG具有抑制肿瘤增殖的作用,其表达缺失可能参与了激素依赖性乳腺癌的进程.     

子宫内膜癌中uPA、ER和PR的表达及其相关性的研究

目的探讨子宫内膜癌中u PA、ER和PR的表达及其相关性。方法采用免疫组化SP法对89例子宫内膜癌和30例正常子宫内膜组织中u PA、ER及PR蛋白的表达进行检测,并根据临床病理特征分析三种蛋白之间的相关性。结果 ER、PR在正常子宫内膜组织中和子宫内膜癌中阳性表达率是逐渐降低的,而u PA的阳性表达率是逐渐升高(P0.05)。u PA、ER、PR的阳性表达率在手术病理分期、肌层浸润深度及有无淋巴结转移中,差异有统计学意义(P0.05)。在子宫内膜癌患者中,u PA的表达与PR的表达呈显著负相关(r=-0.395且P0.05);与ER的表达呈负相关(r=-0.231且P0.05)。结论 ER、PR的减少伴随u PA的高表达参与了子宫内膜癌的发生、发展及转移,并可作为判断子宫内膜癌患者预后及治疗的指标。     

子宫奇异型平滑肌瘤的临床病理分析

目的探讨子宫奇异型平滑肌瘤组织形态、免疫组织化学及生物学行为特征.方法对25例子宫奇异型平滑肌瘤进行瘤体大体及镜下观察;20例行平滑肌肌动蛋白(SMA)、增殖细胞核抗原(PCNA)、雌激素受体(ER)、孕激素受体(PR)免疫组织化学SP和ABC法染色,20例子宫富于细胞性平滑肌瘤作为对照组;并行临床资料分析及跟踪随访.结果临床主要表现为阴道不规则出血、腹痛和盆腔包块,1例合并大量腹水,2例合并妊娠,无应用孕酮类药物者.镜下部分或全部胞核奇异,双核或多核易见,核内多见1至数个较大红染包涵体样物(直径7～26 μm),核分裂象0～2/10高倍视野(HPF).20例奇异型平滑肌瘤做 SMA染色,全部奇异瘤细胞胞质呈肌源性表达,与对照组相同;PCNA染色,观察组15例(75.0%)呈弱阳性,与对照组相比,差异有显著意义(P=0.027);在观察组中18例(90.0%)ER呈阴性表达,表现有ER丢失现象,对照组则全部阳性,两组相比差异有极显著性意义,P＜0.005;PR两组均呈阳性;同时发现大部分核内包涵体样物呈肌源性表达,即SMA阳性.长期随访无复发.结论子宫奇异型平滑肌瘤虽形态奇异,但属良性肿瘤.本组形态学变化与外源性孕酮药物无关,与妊娠关系应予以关注.免疫组织化学表达有一定特征,应与平滑肌肉瘤及恶性潜能待定平滑肌瘤进行鉴别.     

The expression of nuclear estrogen receptor and its relation to cytoplasmic estrogen receptor in breast cancer]

Sixty specimens of breast cancer were assayed with ER-monoclonal antibody by immunocytochemical staining. Twenty-nine (48.33%) were nuclear estrogen receptor positive (ERn+). The number of ERn+ cancer cells decreased in the following sequence: mucinous carcinoma, invasive lobular carcinoma, invasive ductal carcinoma, and papillary adenocarcinoma. Two apocrine carcinomas were ERn-. ERn+ rate was higher in patients over 60 years of age (P less than 0.05). The amount of ERn+ cells was much greater in cancer cells than in the surrounding benign epithelial cells. This phenomenon may indicate that malignant cells are more hormone-dependent than benign cells. The results of immunocytochemical staining and steroid binding assay were compared. By immunocytochemical staining, twenty-four of fifty-seven cases (42.11%) were ERn+ and ERc+. Sixteen cases (28.07%) were ERn- and ERc-. This study showed that in a number of breast cancers ERs were positive in both cytoplasms and nuclei and the concordant rate was 70.18%. In the remaining cases 13 (22.81%), ERs were positive in the cytoplasm, and in 4 cases (7.02%) positive in nuclei only. Additionally, fifty-two out of 60 cases were assayed by 3H-estradiol and 3H-R5020 by means of steroid binding assay. Twenty-seven cases of them (51.92%) showed ERc+ and PRc+, and seventeen cases (32.69%) were ERc- and PRc-. Their correspondent rate was 84.61%.     

IL-6在子宫内膜异位患者血清中的表达及其潜在作用机制研究

目的：探讨IL-6在子宫内膜异位患者血清中的表达及其高表达对子宫内膜异位症腺上皮细胞的作用及潜在机制。方法：ELISA实验检测子宫内膜异位患者血清中IL-6表达;MTT实验检测IL-6对子宫内膜异位症腺上皮细胞增殖影响,Western blot、Transwell实验检测IL-6对子宫内膜异位症腺上皮细胞上皮间质转化的影响;Western blot检测IL-6对细胞中STAT3/BCL6通路蛋白表达的影响;免疫组化检测患者组织中BCL6表达。结果：IL-6在子宫内膜异位患者血清中高表达;IL-6可促进子宫内膜异位症腺上皮细胞增殖和上皮间质转化;IL-6可促进细胞中p-STAT3、BCL6蛋白表达增加;子宫内膜异位患者组织中BCL6高表达。结论：IL-6、BCL6在子宫内膜异位患者血清和组织中普遍高表达,IL-6可能通过激活STAT3/BCL6促进子宫内膜异位症腺上皮细胞增殖及上皮间质转化过程,提示IL-6和BCL6可作为临床诊断治疗子宫内膜异位的新靶标。     

Experimental infection of egg-laying hens with Salmonella enteritidis phage type 4

Chickens were inoculated intravenously with 10(5) or 10(6) organisms. Heavy infection of the ovaries occurred and some infection persisted in this organ for several weeks. Most of the ovarian infections were confined to the interstitial tissues and not to the yolk contained in the large follicles. Infections of the ovary did not result from contamination from infected air sacs. None of 810 eggs laid contained S. enteritidis. Chickens infected orally gave similar results to those following intravenous inoculation although the number of isolations obtained from the caeca and cloaca were higher. S. enteritidis was isolated from two of 633 eggs in which the contents only were cultured and from 36 of 614 eggs in which both shell and contents were cultured. The serum IgG response to oral inoculation was monitored by an ELISA using a whole cell sonicate or lipopolysaccharide antigen. High titres of IgG were detected for 27 weeks after infection when the experiment was terminated. The experiments suggest that most infected eggs laid by 5. enteritidis-infected hens are surface-contaminated and do not result from infected ovaries.     

Transforming growth factor-beta isoforms and receptors in endometriotic cysts of the human ovary.

PROBLEM: The present study examined the presence and cellular distribution of transforming growth factor-beta1, 2, and 3 isoforms and their type I and II receptors in endometriotic cysts of the ovary, relative to their presence in normal endometrial tissue. METHOD OF STUDY: Thirteen control samples of normal endometrium in the proliferative phase and 11 ovarian endometriotic cysts were examined by immunohistochemistry for transforming growth factor-beta1, 2, and 3 isoforms and their type I and II receptors. RESULTS: Immunoreactivity for all ligands and receptors was detected in both normal endometrium and endometriotic cysts. Isoform-specific differences in immunostaining were not detected. Expression of all ligands and receptors was significantly increased in epithelial cells of endometriotic cysts compared with those of normal endometrium. On the other hand, stromal cells in normal endometrium and endometriotic cysts were only faintly immunostained. Inflammatory cells infiltrating among endometriotic stromal cells contained the highest immunostaining intensity for all ligands and receptors. We identified nearly all inflammatory cells as macrophages using a specific antibody. CONCLUSIONS: These findings suggest that macrophages in endometriotic tissue are a major source of transforming growth factor-beta, which may be an important regulator of cell proliferation in endometriotic cysts through paracrine and autocrine actions.     

Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro

The effects of four rounds of ovarian stimulation spaced 1-6 weeks apart on the normality of metaphase II (MII) spindle formation, chromosomal alignment and cytoplasmic organization were examined in intact ovulated mouse oocytes and at MII for oocytes obtained at the germinal vesicle stage from the same ovaries and matured in vitro. The terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling assay was used to identify DNA strand breaks in chromosomes, and histological studies of ovaries between and at each round of ovarian stimulation were performed. The results demonstrate a progressive and significant increase in the frequency of spindle defects with each round of ovarian stimulation, including those spaced weeks apart. Oocytes with spindle defects were also characterized by the occurrence of detached chromosomes and cytoplasmic asters. In contrast, in-vitro matured oocytes derived from the same ovaries were normal. No evidence of DNA strand breaks with repeated rounds of ovarian stimulation was detected in ovulated or in-vitro matured oocytes. The development and persistence of nodules of hypertrophied granulosa in regions where follicular growth occurs suggest that a progressively increasing proportion of oocytes in the ovulatory pathway may experience an intrafollicular milieu that has negative consequences for competence. The results are discussed with respect to ovarian and oocyte biological ageing and possible adverse implications for human oocyte competence with repeated hyperstimulation.     

Immune response in rabbit ovaries following infection of a recombinant myxoma virus expressing rabbit zona pellucida protein B

In this study, we investigated the autoimmune response in rabbit ovaries following infection with a recombinant myxoma virus expressing rabbit zona pellucida protein B (MV-ZPB). A specific IgG antibody response to ZPB was elicited in the serum of infected rabbits and the antibody strongly bound to the zona pellucida of oocytes in secondary and tertiary follicles. T cell infiltration in the ovary was detected in a small proportion of the infected rabbits. In spite of this, the mean number of preovulatory and tertiary follicles in the ovary was significantly reduced at 30 days postinfection compared with that of the infected and uninfected controls. Histological analysis revealed that the cortex and medulla of these ovaries had accumulated a large number of probably luteinized cells and there were no follicles in these areas, indicating the ovaries were in a severe pathological condition. The data suggest that the delivery of ZP antigens using a recombinant myxoma virus is a prospective way to develop immunocontraceptive vaccines for rabbit population control, but that more understanding of the kinetics of the autoimmune response induced by viral delivery is needed.     

Does laparoscopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles

BACKGROUND: Residual ovarian function after laparoscopic excision of endometriotic ovarian cysts is a major and still unsolved topic. Ultrasonographic evaluation of ovarian response to ovulation stimulation represents a simple yet poorly employed tool to assess residual ovarian function after surgery. METHODS: Data from patients referred for IVF or ICSI between January 2001 and December 2002 were reviewed. Patients were included who previously underwent laparoscopic excision of a monolateral endometriotic ovarian cyst. The operated ovary and contralateral intact ovary were compared in terms of number of follicles with a mean diameter >15 mm at the time of hCG administration. Basal volume of the two ovaries before initiating stimulation was also compared. A paired Student's t-test was used to investigate differences between the two ovaries. RESULTS: In total, 32 patients and 46 cycles were identified. The mean (+/- SD) number of follicles >15 mm was 4.2 +/- 2.5 in the control ovary and 2.0 +/- 1.5 in the previously operated ovary (P < 0.001); this corresponded to a mean reduction of 53% (95% CI 35-72%) but did not seem to be related to the dimension of the excised ovarian cyst. The basal volume of the operated ovaries was also statistically significantly diminished, though this reduction was less relevant. CONCLUSIONS: Excision of endometriotic ovarian cysts is associated with a significant reduction in ovarian reserve. Further studies are required to clarify whether the damage is related to the surgical procedure or to the previous presence of a cyst.     

An association of IgG anti-laminin-1 autoantibodies with endometriosis in infertile patients

BACKGROUND: Laminin-1, a multifunctional glycoprotein of the basement membrane, is thought to be important in embryogenesis, embryonic implantation, and placentation. We recently showed that serum IgG anti-laminin-1 autoantibodies (auto-Abs) are associated with recurrent first-trimester miscarriages. The present study assessed the clinical significance of anti-laminin-1 Abs with infertility, accompanied with or without endometriosis. METHODS: Sixty-eight infertile patients who underwent laparoscopy or laparotomy and 39 healthy non-pregnant women were tested for IgG anti-laminin-1 Abs. The association between the Abs and endometriosis was analysed. The presence of laminin-1 mRNA was detected in endometriotic lesions. RESULTS: Twenty infertile patients were positive for anti-laminin-1 Abs. The Ab levels in those patients were significantly higher than those in healthy non-pregnant women (P = 0.0005). The presence of the Abs was significantly associated with endometriosis in those patients (P = 0.0096). The Abs recognized a particular domain, i.e., the laminin-alpha1 chain G domain. mRNA encoding laminin-alpha1, -beta1, and -gamma1 chains was expressed in 90% of endometriotic lesions. CONCLUSIONS: IgG anti-laminin-1 Abs were significantly associated with endometriosis in infertile patients. The Abs might be clinically important in the development of autoimmune-mediated reproductive failures and the assessment of the Abs may provide a novel non-invasive diagnosis of endometriosis.     

Progesterone receptors in human oestrogen target tissues

The levels of specific oestrogen and progesterone receptors have been measured in myometrial, endometrial and vaginal tissues obtained from 18 women between the ages of 28–73 yr.High speed cytosols of the three tissues were incubated at four different concentrations of specific ligands: E₂ for the oestrogen receptor (ERc) and Org-2058 for the progesterone receptor (PgRc). Separation of bound and free hormones was done by dextran-coated charcoal; data were analysed according to Scatchard.In the myometrium and endometrium both PgRc and ERc were found. In the vaginal tissues obtained from the same patients only ERc was present. There was no evidence of specific progesterone receptors in the vagina. Both clinical and histological findings indicate that the vagina is an oestrogen-sensitive organ. Therefore, it is surprising that progesterone receptors, which are considered to be a specific response of oestrogen target tissue, are absent in the human vagina.This finding suggests that the induction of the progesterone receptors is not a specific response to oestrogen stimulation in the human vagina.