雌激素受体相关受体亚型在卵巢癌中的表达及其与预后的关系

目的探讨雌激素受体相关受体（ERRs）亚型α、β、γ在卵巢癌中的表达及其与预后的关系。方法激光共聚焦显微镜观察ERRα蛋白在卵巢癌细胞株SKOV3和OVCAR3细胞内的定位。RT-PCR技术检测33份卵巢癌组织以及12份正常卵巢组织中3种ERRs亚型的mRNA表达,并结合临床病理指标分析其预后情况。结果ERRα蛋白主要分布于SKOV3和OVCAR3细胞的细胞核内。卵巢癌组织中ERRα mRNA的阳性表达率（58％）和ERRγ mRNA的阳性表达率（48％）显著高于正常卵巢组织（分别为17％和33％,P〈0．05）;ERRβ mRNA的阳性表达率在卵巢癌组织和正常卵巢组织中都很低（分别为9％和0）,两者比较,差异无统计学意义（P=0．795）。ERRα mRNA的阳性表达与卵巢癌的手术病理分期（r=0．639,P=0．017）、病理分级（r=0．520,P=0．022）呈正相关。ERRα mRNA阳性表达的卵巢癌患者,其中位数整体生存时间（19．0个月）明显短于ERRα mRNA阴性表达患者（31．5个月,P=0．015）,但两者间的无瘤生存时间（分别为12．6和14．5个月）比较,差异无统计学意义（P=0.820）;ERRγ mRNA阳性表达患者的中位数无瘤生存时间（18．0个月）显著长于ERRγ mRNA阴性表达患者（13．5个月,P=0．020）,但两者间中位数整体生存时间（分别为23．4和19．6个月）比较,差异无统计学意义（P=0．093）。结论ERRα蛋白主要表达于卵巢癌细胞核内。ERRα mRNA高表达与卵巢癌患者的预后差有关,而ERRγ mRNA高表达可能提示患者预后较好。     

Different expression of estrogen receptors alpha and beta in human myometrium and leiomyoma during the proliferative phase of the menstrual cycle and after GnRHa treatment.

Uterine leiomyomas (uterine fibroids) are sex-steroid dependent benign tumors. Limited knowledge is available regarding the role of estrogen and their receptors in the regulation of fibroids in premenopausal women, and in their shrinkage after treatment with a gonadotropin-releasing hormone analogue (GnRHa). The expression of the two subtypes of the estrogen receptor (ER), ER alpha and ER beta, was studied in leiomyoma and homologous myometrium from women in the proliferative phase of the menstrual cycle and from women treated with GnRHa. The mRNA levels of ER alpha and ER beta were monitored by solution hybridization and in situ hybridization, and receptor proteins were detected and localized by immunohistochemistry. Both ER alpha and ER beta were present in the leiomyomas and homologous myometrium. The ER alpha mRNA level in the leiomyomas was higher than in the surrounding myometrium. The ER beta mRNA level was lower than that of ER alpha in both groups. ER beta immunoreactivity was lower in leiomyomas when compared with the myometrium after GnRHa treatment, while ER alpha was higher in the leiomyomas. The present results imply that the increased ratio of ER alpha/ER beta observed in the fibroids after GnRHa treatment could reflect or be the cause of the shrinkage of the leiomyoma, which is the clinical outcome of this treatment.     

Cytoplasmic estrogen receptors in carcinoma of the uterine cervix

The concentration of cytoplasmic estrogen receptors (ER) in cancer of the uterine cervix was measured in 30 cases (28 squamous cell carcinomas and 2 adenocarcinomas). The mean ER concentration in squamous cell carcinoma was 19.3 +/- 26.0 fmol/mg cytosol protein; for pre- and postmenopausal women 6.82 +/- 9.86 and 28.6 +/- 30.1 fmol/mg protein, respectively, were found, the latter being significantly higher. When 'ER-positive' was defined as concentrations greater than 10 fmol/mg protein, 12 of the 28 cases (43%) were found to be ER-positive. There were no significant differences between the ER concentrations of clinical stage I and II squamous cell carcinomas (19.2 +/- 24.2 and 20.9 +/- 27.2 fmol/mg, respectively). ER were detectable in the cervical tissue from all of the control cases of myoma of the uterus. There were, however, no differences in the ER content between the proliferative and secretory phases, but the concentration in premenopausal women was significantly lower than that in postmenopausal women. In comparison with the controls, the mean ER level in both pre- and postmenopausal women with squamous cell carcinoma was significantly lower, due to the fact that ER were not detectable in 57% of these cases. Both cases of cervical adenocarcinoma were ER-positive.     

The concentration of estrogen receptors in rabbit uterine myocytes decreases in culture.

OBJECTIVE: The purpose of this study was to determine whether the concentration of estrogen receptors in cultured myocytes is preserved after dispersion. STUDY DESIGN: Primary myocytes were prepared from rabbit myometrium by collagenase dispersion after removing the endometrium and were isolated with Percoll density gradients. The cells were assayed for estrogen receptor concentration at intervals after dispersion by means of a whole-cell binding assay. Unpaired t test was used for comparisons. RESULTS: The concentration of estrogen receptors on the first day after dispersion was 12,058 +/- 1096 sites per cell (mean +/- SEM) and decreased to 4389 +/- 1223 site per cell within 9 to 14 days after dispersion (63% decline, p < 0.001). A similar decrease was observed when 2 nmol/L estradiol was present in the medium. CONCLUSION: The concentration of estrogen receptors in isolated rabbit uterine myocytes decreases after dispersion. This may partly explain the difficulty of demonstrating in vitro estrogen effects on myocytes, which are well established in vivo.     

Comparison of the genetic alterations in two epithelial collision tumors of the uterine cervix. A report of two cases.

In a minority of cervical carcinomas, a distinct adenocarcinoma and squamous cell carcinoma component can be recognized. These tumors are considered collision tumors; the differential diagnosis is adenosquamous carcinoma. To investigate whether the squamous and adenocarcinoma component are of multiclonal or monoclonal origin, we used loss of heterozygosity (LOH) as a method to establish clonality. Each tumor component of two tumors with a distinct adenocarcinoma and squamous cell carcinoma component were microdissected and the presence of LOH was studied for nine chromosomes, i.e., 1, 2, 3, 6, 11, 15, 17, 18, and X, which are known to contain frequent LOH in cervical cancer. The tumor of patient AK13 showed identical LOH in both the adenocarcinoma and squamous cell carcinoma tissue with various microsatellite markers on chromosomes 1, 2, 6, 18, and X. For markers on chromosomes 3 and 15, different LOH patterns were found in both components. The squamous epithelium showed LOH on chromosome 3, whereas the adenocarcinoma component had LOH on chromosome 15. For patient AK18 the LOH pattern on chromosomes 6p and 17 was the same in the adenocarcinoma and the squamous cell carcinoma component. The adenocarcinoma component showed additional LOH on chromosomes 6q and chromosome 11q. The tumor of patient AK18 showed common boundaries of LOH in both components on chromosome 17q, between markers D17S578 and D17S250. In conclusion, the squamous cell carcinoma and adenocarcinoma components in both tumors most likely have one cell of origin because many genetic alterations are the same in each component. The presence of genetic changes uniquely associated with one of the tumors favors a diversion of developmental pathways.     

Mucinous tumors of the appendix presenting as primary tumors of the ovary. Report of two cases

Primary tumors of the appendix are rare and most of them are unrecognized preoperatively, presenting as appendicits, pelvic masses or with no typical abdominal pain. Two cases of mucinous tumors of the appendix presenting as primary ovarian tumors are described. It is important for the gynecologist-oncologist to include mucinous tumors of the appendix into the differential diagnosis of any case of mucinous ovarian tumor and peritoneal pseudomyxoma, especially when these tumors are associated with extraovarian disease.     

阴道前壁膨出患者阴道组织中雌激素受体α和β亚型的表达

目的 了解阴道前壁膨出（AVP）患者阴道组织中雌激素受体（ER）α、β亚型的表达情况,探讨其与盆腔器官脱垂（POP）发病的关系。方法 选取1999年7月-2004年7月在北京大学人民医院手术治疗的AVP患者40例（AVP组）,其中绝经前7例,绝经后33例。对照组为同时期手术的Ⅰb1～Ⅱb期宫颈鳞癌患者17例（无盆腔器官膨出症状）,其中绝经前9例,绝经后8例。应用免疫组化方法检测阴道前壁组织中鳞状上皮、黏膜固有层、肌层3个部位的ERa和ERβ表达水平（以阳性细胞率及阳性染色强度的评分判断ER的表达水平）,进行半定量分析及统计学检验。结果 （1）ERα、ERβ在AVP组患者阴道组织中鳞状上皮、黏膜固有层、肌层均有表达。（2）AVP组绝经前患者阴道组织中ERα表达水平分别为：鳞状上皮（5．3±0．8）分、黏膜固有层（3．2±2．1）分、肌层（3．0±1．5）分,绝经后患者分别为（4．6±1．2）、（4．1±1．2）、（3．7±1．4）分,绝经前、后患者不同部位分别比较,差异均无统计学意义（P〉0．05）;对照组患者的阴道组织中ERα表达水平在绝经前、后比较,差异也无统计学意义（P〉0．05）。（3）ERβ表达水平在绝经前、后AVP组患者阴道组织中比较,差异无统计学意义（P〉0．05）;而对照组绝经前患者阴道组织中ERB表达水平分别为：鳞状上皮（4．2±0．5）分、黏膜固有层（2．6±1．4）分、肌层（2．4±0．8）分,绝经后患者分别为（2．6±1．3）、（1．1±0．7）、（1．4±0．9）分,对照组绝经后患者阴道组织中ERB的表达水平下降（P〈0．05）。（4）AVP组绝经后患者阴道组织中ERB表达水平分别为：鳞状上皮（4．1±1．6）分、黏膜固有层（3．4±1.7）分、肌层（3．3±112）分,绝经后AVP组患者阴道组织各部位ERβ的表达水平高于绝经后对照组患者相应部位（P〈0．05）;而绝经后患者ERα在阴道组织中的表达水平,AVP组与对照组比较,差异无统计学意义（P〉0．05）。结论 无论绝经前、绝经后AVP患者,阴道组织都存在ERα、ERβ的表达。AVP患者阴道组织中ERβ表达在绝经后未下降,且较对照组绝经后患者表达增加,而ERα无明显变化。     

Expression of alpha6 and beta4 integrin subunits throughout the menstrual cycle: no correlation with uterine receptivity.

OBJECTIVE: To compare the expression of alpha6 and beta4 integrin subunit levels throughout the menstrual cycle in the endometrium of healthy women and infertile women. DESIGN: Prospective study. SETTING: An academic teaching hospital. PATIENT(S): Endometrium was collected from 58 women, including healthy subjects (n = 28) and patients undergoing diagnostic testing for infertility (n = 30). INTERVENTION(S): Endometrial biopsies were performed throughout the menstrual cycle in healthy women and infertile women. MAIN OUTCOME MEASURE(S): Immunohistochemical staining intensity of alpha6 and beta4 using the semiquantitative immunohistochemical score, compared using regression analysis and analysis of variance with Scheffé's correction. RESULT(S): There was no correlation between menstrual cycle phase and endometrial integrin subunit alpha6 or beta4 on glandular or luminal epithelium. Even women with identified luteal phase defects had indistinguishable patterns of expression for these integrin subunits during the window of implantation. CONCLUSION(S): The integrin subunits alpha6 and beta4 are expressed uniformly throughout the menstrual cycle on glandular and luminal epithelium. These integrins may have a housekeeping role in anchoring endometrial epithelium and do not appear to be useful markers of uterine receptivity.