肿瘤坏死因子α及转化生长因子β在子宫腺肌病中的表达

目的:研究肿瘤坏死因子α(TNF-α)和转化生长因子β(TGF-β)在和子宫腺肌病中的表达及其临床意义。方法:应用免疫组化SABC技术检测正常子宫组织11份和子宫腺肌病组织33份蜡封包埋切片中TNFα与TGFβ的组织定位和表达。结果:正常子宫和子宫腺肌病组织中均存在TNFα与TGFβ的表达;正常子宫内膜腺体细胞中TNF-α与TGF-β表达强度分别高于子宫肌层和间质,分泌期高于增生期,并呈周期性变化;在子宫腺肌病组织中,TNFα与TGF-β在原位内膜中的表达强度,分泌期高于增生期,并呈周期性变化;TNF-α与TGF-β在异位子宫内膜中的表达强度分别高于原位内膜和正常子宫内膜,腺体表达强度分别高于子宫肌层和间质。结论:TNF-α和TGF-β的表达受卵巢性激素的调控;其在子宫腺肌病异位内膜中的高表达可能是子宫腺肌病发生的病理机制之一。     

血管内皮生长因子在子宫腺肌病中的表达及意义

目的:研究血管内皮生长因子(VEGF)在子宫腺肌病中的组织定位和表达,以探讨VEGF与子宫腺肌病发生的关系。方法:用免疫组化染色法检测13例子宫腺肌病患者在位及异位子宫内膜中VEGF的表达。结果:在位和异位子宫内膜组织均有VEGF阳性染色。经计算机扫描图像处理,异位组织的腺上皮和间质VEGF表达高于在位组织的腺上皮及间质(P<0.05)。结论:高表达的VEGF可能与子宫腺肌病的发生和发展有关。     

bcl-2蛋白在子宫腺肌病组织中的表达

目的　探讨bcl 2蛋白表达在子宫腺肌病发生中的病理生理作用及其临床意义。方法　应用免疫组织化学法 ,检测 16例正常子宫及 32例子宫腺肌病患者子宫组织中bcl 2基因蛋白的组织定位和表达强度 ,对比其差异。结果　增殖期 ,bcl 2在正常子宫内膜及子宫腺肌病患者子宫在位、异位子宫内膜腺体中的表达强度分别为 (2 .0± 0 .3)、(2 .5± 0 .1)和 (3.0± 0 .1)分 ( x±s x,下同 ) (P <0 .0 5 ) ,在间质中的表达强度分别为 (0 .4± 0 .1)、(1.1± 0 .2 )和 (1.0± 0 .2 )分 (P <0 .0 5 ) ;分泌期 ,bcl 2在正常子宫及子宫腺肌病患者在位、异位子宫内膜腺体中的表达强度分别为 (0 .9± 0 .2 )、(1.3± 0 .2 )和 (1.7± 0 .2 )分 (P <0 .0 5 ) ,在间质中的表达强度分别为 (1.1± 0 .2 )、(0 .9± 0 .2 )和 (1.0± 0 .2 )分 (P >0 .0 5 )。在平滑肌中表达强度无明显变化。结论　bcl 2基因在子宫腺肌病子宫内膜中过度表达所致的细胞凋亡减弱 ,可能是子宫腺肌病发生的机理之一     

神经细胞黏附因子在子宫腺肌病病灶中的表达及意义

目的:检测神经细胞黏附因子(NCAM)在子宫腺肌病在位内膜及异位内膜中的表达,探讨NCAM在子宫腺肌病发病中的作用。方法:采用免疫组化法检测40例子宫腺肌病标本在位内膜与异位内膜组织中NCAM的表达情况(分泌期与增生期各20期),并与20例正常子宫内膜标本进行比较。采用0~10级NRS疼痛评价量表对子宫腺肌病患者痛经程度进行评分,并与相应患者NCAM染色情况进行比较。结果:NCAM在40例子宫腺肌病在位内膜和异位内膜及19例正常内膜腺上皮中均有表达,1例正常内膜无表达,间质中无表达。异位内膜组织中NCAM表达明显高于在位内膜和正常对照组(P0.01)。在位内膜组织分泌期NCAM表达含量高于增生期(P0.05)。子宫腺肌病异位病灶NCAM表达与患者痛经程度呈正相关(r=0.84,P0.01)。结论:NCAM可能参与子宫腺肌病的发病过程,并参与子宫腺肌病痛经的发生发展,但具体分子机制尚需进一步研究。     

子宫腺肌病的激素受体免疫组织化学分析

对２４例子宫腺肌病病灶内腺上皮和２０例对照病例的子宫内膜激素受体行免疫组织化学分析，以研究正常子宫内膜与子宫腺肌病病灶内的腺上皮雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、雄激素受体（ＡＲ）、卵泡刺激素受体（ＦＳＨ－Ｒ）、黄体生成素受体（ＬＨ－Ｒ）和垂体泌乳素受体（ＰＲＬ－Ｒ）的表达。结果：子宫腺肌病病灶内的腺上皮ＬＨ－Ｒ、ＰＲＬ－Ｒ、ＰＲ和ＡＲ的水平明显高于正常子宫内膜腺上皮。     

子宫腺肌病深肌层异位内膜性激素及性激素受体测定的临床意义

选择子宫腺肌病住院手术病人４５例，采用ＡＢＣ免疫组化法测定石蜡固定包埋的深肌层异位内膜标本中雌二醇（Ｅ２）、孕激素（Ｐ）、睾酮（Ｔ）、雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、雄激素受体（ＡＲ）。另取１７份增生期原位内膜作对照，分析性激素及性激素受体与临床表现的关系。研究发现子宫深肌层异位内膜有Ｅ２、Ｐ、Ｔ、ＥＲ、ＰＲ、ＡＲ阳性细胞存在，其中ＥＲ、ＡＲ阳性表达率显著高于原位内膜。但性激素及性激素受体的阳性率与子宫腺肌病的临床症状、病程和子宫体积无明显关系。提示：子宫腺肌病的发生、发展除了与雌激素有关外，还与孕激素、雄激素有关，同时应用抑制多种受体的药物可能是治疗子宫腺肌病的途径之一。     

子宫腺机病的激素受体免疫组织化学分析

对２４例子宫腺肌病病灶内腺上皮和２０例对照病例的子宫内膜激素受体行免疫组织化学分析，以研究正常子宫内膜与子宫腺肌病病灶内的腺上皮雌激素受体（ＥＲ），孕激素受体（ＰＲ），雄激素受体（Ａ），卵泡刺激素受体（ＦＳＨ－Ｒ）黄体生成受体（ＬＨ－Ｒ）和垂体泌乳素受体（ＰＲＬ－Ｒ）的表达，结果：子宫腺肌病病灶内的腺上皮ＬＨ－Ｒ，ＰＲＬ－Ｒ，ＰＲ和ＡＲ的水平明显高于正常子宫内膜腺上皮。     

表皮生长因子受体在子宫内膜、早孕蜕膜及滋养细胞中的表达

目的了解表皮生长因子受体（ＥＧＦＲ）在子宫内膜细胞分化及发育中的作用。方法采用免疫组织化学及逆转录聚合酶链反应（ＲＴＰＣＲ）技术测定５８例正常子宫内膜（３２例增生期,２６例分泌期）与２６例早孕蜕膜。结果ＥＧＦＲ存在于正常子宫内膜、早孕蜕膜腺体及间质细胞的细胞膜、核膜及胞浆内,分布均匀。ＥＧＦＲ还位于早孕蜕膜腺体及间质细胞核内。正常子宫内膜ＥＧＦＲ的表达,腺体部分高于间质部分（Ｐ＜０．０５）,ＥＧＦＲ在增生期及分泌期子宫内膜腺体的表达差异无显著性（Ｐ＞０．０５）,但ＥＧＦＲ在早孕蜕膜组织中的表达明显高于增生期及分泌期（Ｐ＜０．０５）。ＥＧＦＲ在间质细胞的表达,早孕蜕膜高于分泌期内膜,而增生期内膜则表达最低（Ｐ＜０．０５）。ＥＧＦＲｍＲＮＡ的表达从弱到强依次为增生期、分泌期、蜕膜、滋养细胞,增生期与分泌期比较,差异无显著性（Ｐ＞０．０５）,早孕蜕膜较分泌期及增生期明显增加（Ｐ＜０．０５）,滋养细胞ＥＧＦＲｍＲＮＡ的表达明显高于增生期、分泌期及早孕蜕膜（Ｐ＜０．０５）。结论ＥＧＦＲ存在于各期子宫内膜中,其表达在正常月经周期中无明显变化,但在早孕蜕膜、滋养细胞中的表达明显高于增生期及分泌期内膜     

Akt和NF-κB在子宫腺肌病中的表达及其意义

目的:研究Akt和NF-κB在子宫腺肌病病灶中的表达,探讨其在子宫腺肌病发生发展中的意义。方法:采用免疫组化SP法检测子宫腺肌病病灶(30例)、在位内膜(27例)、正常子宫内膜(20例)标本中Akt、P-Akt及NF-κB蛋白的表达并进行比较。结果:Akt、P-Akt蛋白在子宫腺肌病异位内膜的腺上皮细胞中的表达强度显著高于在位内膜(P<0.05)和正常子宫内膜(P<0.01),其在位内膜腺上皮细胞中的表达强度显著高于正常子宫内膜(P<0.01);间质细胞中Akt、P-Akt蛋白的表达,异位和在位内膜明显高于正常内膜,异位内膜和在位内膜中两者的表达无显著性差异。NF-κB蛋白表达于胞核和胞浆中,在腺上皮细胞中的表达,异位内膜显著高于在位内膜,在位内膜显著高于正常子宫内膜(P<0.05);间质细胞中,NF-κB蛋白的表达各组间无显著性差异。NF-κB与P-Akt在子宫腺肌病病灶、在位子宫内膜和正常子宫内膜中的表达呈正相关(r=0.626,P<0.01)。结论:NF-κB与Akt在子宫腺肌病病灶中呈高表达,其可能参与子宫腺肌病的发生与发展过程。     

芳香化酶P450在雌激素依赖性疾病病变内膜中的表达

目的探讨芳香化酶P450（P450arom）在子宫内膜增生症、子宫腺肌病等雌激素依赖性疾病病变内膜中的不同表达。方法采用免疫组化方法分别测定子宫腺肌病异位内膜（Ⅰ组）、子宫腺肌病在位内膜（Ⅱ组）、子宫内膜增生症内膜（Ⅲ组）、正常子宫内膜（Ⅳ组）四组不同内膜中P450arom的表达。根据阳性率和表达强度进行量化评分（免疫组化评分）。结果 ①P450arom在子宫腺肌病异位、在位、子宫内膜增生症内膜中均阳性表达，但在正常子宫内膜无表达，P450arom在异位子宫内膜表达强度明显高于在位子宫内膜、增生症子宫内膜（P〈0．05）；异位子宫内膜病灶周围肌肉组织中也有P450arom表达；②P450arom在子宫内膜异位症内膜的增殖期和分泌期表达，差异无统计学意义（P〉0．05）。结论 ①雌激素限速酶P450arom是子宫腺肌病、子宫内膜增生症等雌激素依赖性疾病发生、发展的重要激素，局部分子水平代谢紊乱可能导致疾病发生。②内膜P450arom检查不能作为盆腔子宫内膜异位症诊断方法，但可作为雌激素依赖性疾病筛选方法。     

Aberrant immunoreactivity of deoxyribonucleic Acid methyltransferases in adenomyosis

Objectives: To investigate the expression and localization of deoxyribonucleic acid methyltransferases (DNMTs) in women with and without adenomyosis. Study Design: Ectopic and homologous eutopic endometrium from 50 women with adenomyosis and endometrium from 18 age- and menstrual phase-matched women without adenomyosis were used for immunohistochemical analysis. Tissue sections were immunostained with DNMT1, DNMT3A, and DNMT3B. Microscopic evaluation to assess the presence and localization of DNMT1, DNMT3A, and DNMT3B throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis was performed, and comparison with normal endometrium was made. Results: Compared with normal endometrium, immunoreactivity to DNMT1 and DNMT3B was higher in ectopic endometrium, while DNMT3A staining levels were significantly reduced in both eutopic and ectopic endometrium. DNMT1 immunoreactivity in eutopic endometrium was positively associated with heavier menses. Increased DNMT3B immunoreactivity in ectopic, but not eutopic, endometrium was associated with the severity of dysmenorrhea. Conclusions: The immunoreactivity to DNMTs in adenomyosis differs significantly from that in normal endometrium, suggesting that adenomyosis may be an epigenetic disease. The finding that DNMT3B correlates with the severity of dysmenorrhea suggests that DNMTs may be involved in adenomyosis-caused dysmenorrhea and its severity. Thus, therapeutics based on epigenetic rectification may hold promise in the management of adenomyosis.     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis.

OBJECTIVES: To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. PATIENT AND METHODS: This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. RESULTS: Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. CONCLUSION: Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Expression of heme oxygenase in the eutopic and ectopic endometrium in patients with adenomyosis

Heme oxygenase (HO) is the rate-limiting enzyme that catalyzes the degradation of heme into iron, carbon monoxide, and biliverdin. This enzyme has important functions in cellular homeostasis, including the regulation of oxidative load, apoptosis, and inflammation. Two isoforms of HO, the inducible HO-1 and the constitutive HO-2, are expressed and are known to play a role in the normal human endometrium throughout the menstrual cycle, but there is little evidence for HO expression and behavior in adenomyosis, which is the occurrence of intramural ectopic endometrial tissue. The aim of this study was to investigate the presence and localization of the two HO isoforms in both eutopic and ectopic endometrium of women with adenomyosis during the menstrual cycle. The oxidative stress and apoptosis related to HO-1 expression were also assessed. The expression of HO-1 and HO-2 in both eutopic and ectopic endometrium was confirmed, and their levels in the ectopic endometrium were lower than those in the eutopic endometrium. The cyclic variability of HO expression was lost in the ectopic endometrium during the menstrual cycle, whereas this variability was apparent in the eutopic endometrium. Moreover, HO-1 expression corresponded to apoptotic events in the eutopic endometrium. Constitutive HO-2 expression corresponded to endometrial proliferation and degradation. These results reveal that both HO-1 and HO-2 contribute little in the pathophysiology of adenomyosis.     

Expression and possible role of interleukin-10 receptors in patients with adenomyosis

Objective

To investigate the expression and potential roles of interleukin-10 receptor 1 (IL-10R1) and interleukin-10 receptor 2 (IL-10R2) in adenomyosis.

Study design

This prospective study examined 33 women with histologically proven adenomyosis and 21 women without adenomyosis who had undergone hysterectomy for non-endometrial pathology. Comparative immunohistochemistry was used to evaluate the expression and localization of IL-10R1 and IL-10R2. Tissue sections were immunostained with goat anti-human interleukin-10 receptor alpha and rabbit anti-human interleukin-10 receptor beta antibodies. The presence and localization of IL-10R1 and IL-10R2 were evaluated microscopically throughout the menstrual cycle in eutopic and ectopic endometrial tissues of women with adenomyosis, and the results were compared with those for normal endometrium.

Results

IL-10R1 and IL-10R2 were mainly expressed by epithelial cells in both women with adenomyosis and controls. Epithelial expression of IL-10R1 and IL-10R2 was higher in adenomyotic samples than in eutopic endometrium of women with adenomyosis or normal endometrium. Moreover, epithelial expression of IL-10R1 was higher in eutopic endometrium of women with adenomyosis than in normal endometrium. Epithelial expression of IL-10R1 showed cyclic variation in eutopic endometrium of women with adenomyosis and normal endometrium, with elevated expression in secretory-phase tissues compared with proliferative-phase tissues.

Conclusions

Intrinsic abnormalities concerning IL-10 and IL-10 receptors may be present in eutopic and ectopic endometria of women with adenomyosis. These findings suggest that IL-10 receptors may be involved in the immunotolerant and/or anti-inflammatory process of adenomyosis.     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis

Objectives.?To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle.

Patient and methods.?This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods.

Results.?Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle.

Conclusion.?Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis.

OBJECTIVE: To determine the expression of superoxide dismutase (SOD) in the endometrium during the menstrual cycle in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of SOD in endometrial tissues using the monoclonal antibody. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): The subjects were divided into three groups: 36 patients with endometriosis, 38 patients with histologically proven adenomyosis, and 47 fertile control subjects. INTERVENTION(S): Endometrium was biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score for endometrial cells. RESULT(S): The analyses revealed phase-dependent changes in the expression of SODs in the glandular and surface epithelia during the menstrual cycle in fertile controls. Specifically, the expression of copper, zinc SOD was weakest in the early and midproliferative phases, then gradually increased, and was most marked in the early and midsecretory phases. The expression of manganese SOD reached a peak in the late secretory phase. The expression of both SODs in endometriosis and adenomyosis was persistently higher than the control levels throughout the menstrual cycle. CONCLUSION(S): The exaggerated expression of both SODs in the endometrium throughout the menstrual cycle suggests that superoxide plays a key role in infertility in endometriosis and adenomyosis.     

Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

OBJECTIVE:To determine the expression of glutathione peroxidase (GPx) in the eutopic and ectopic endometria during the menstrual cycle in endometriosis and adenomyosis. DESIGN:Immunohistochemical identification of GPx in endometrial tissues identified using the polyclonal antibody. SETTING:Department of obstetrics and gynecology in a university hospital. PATIENT(S):One hundred fourteen women divided into three groups: 33 patients with endometriosis, 34 patients with adenomyosis, and 47 fertile control subjects. INTERVENTION(S):Endometrium biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S):Endometrial cells: semiquantitative immunostaining (evaluation nomogram) score. RESULT(S):The analyses revealed phase-dependent changes of GPx expression in the surface and glandular epithelia in the eutopic endometrium during the menstrual cycle in the fertile controls, i.e., the expression was weak in the early proliferative phase, gradually increased, was most marked in the early secretory phase, and decreased thereafter. The expression of GPx in the eutopic endometrium in endometriosis lost the variation during the menstrual cycle. The expression of GPx in adenomyosis was persistently marked over the control levels throughout the menstrual cycle. CONCLUSION(S):The aberrant expression of GPx in the eutopic endometrium throughout the cycle suggests a pathological role in endometriosis and adenomyosis.     

子宫腺肌症中缩宫素受体的分布及其与痛经间的关系研究

目的 探讨缩宫素受体（OTR）在子宫腺肌症（AM）在、异位内膜中的分布及其与临床痛经之间的关系,研究OTR在疾病发病机制中的作用。方法 采用免疫组织化学方法检测28例腺肌症病灶组织、28例在位内膜组织中OTR的表达,并和18例正常子宫内膜组织作对照。结果 AM中OTR在腺肌症病灶中的表达（92.8%）高于在位子宫内膜中的表达（78.6%）,P〈0.05,并均高于正常子宫内膜（50%）。表达强度差异有统计学意义（P〈0.05）。其表达在在位子宫内膜和正常子宫内膜中增殖期高于分泌期;而异位病灶则缺乏这样的差异性。重度痛经组比轻度痛经组OTR的表达增高。结论 在AM中的在位及异位内膜中,OTR均有高表达,可能参与疾病的发生发展机制。OTR的表达与痛经症状相关,推测OTR系统与腺肌症相关症状痛经有关系。     

Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

OBJECTIVE: To investigate the expression of xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of xanthine oxidase in endometrial tissues by using polyclonal antibody. SETTING: University hospital. PATIENT(S): Thirty-four women with endometriosis, 34 women with adenomyosis, and 44 fertile control women. INTERVENTION(S): Biopsy samples were obtained from the endometrium throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score of endometrial cells. RESULT(S): The level of xanthine oxidase expression in the glandular epithelium of control varied according to menstrual phase, but no such variation in expression was seen in endometriosis. Variation in xanthine oxidase expression was observed during the menstrual cycle in patients with adenomyosis; this variation differed completely from that in controls. Xanthine oxidase expression was found in ectopic endometrial tissue in all cases. The mean evaluation nomogram levels in the glandular epithelium in adenomyosis tissue were as high as those in the early secretory phase in the eutopic endometrium. CONCLUSION(S): Aberrant expression of xanthine oxidase in eutopic and ectopic endometrium appears to play a pathologic role in endometriosis and adenomyosis.