孕激素受体及B亚型在子宫内膜腺癌的表达及意义

目的 研究子宫内膜癌组织中孕激素受体及B亚型的分布及表达,探讨其临床意义。方法选取30例子宫内膜癌手术标本和10例正常增生期子宫内膜标本,石蜡切片,采用免疫组化方法,测定组织孕激素受体亚型的分布及表达。结果孕激素受体及B亚型均为核受体。PR在子宫内膜癌组织中表达的阳性率为93.33％,对照组的阳性率为100.00％,两者比较差异无显著性(P>0.05);PRB在子宫内膜癌组织中表达的阳性率为50.00％,与对照组比较差异有显著性(P<0.05)。PR的阳性率表达与分化程度无相关性,肿瘤不同分化程度的PRB阳性表达率有显著差异,分化高的:PRB阳性率高,分化低的PRB阳性率低。PR及PRB的阳性表达在临床分期I～Ⅲ各组间差异均无显著性(P值均>0.05)。结论hPR与hPRB为核受体,在子宫内膜腺癌组织中的阳性表达有所不同,PRB的阳性表达与病理分级有一定的关系,故测定PR、PRB在内膜癌的表达对指导其内分泌治疗、预测预后有一定的意义。     

卵巢上皮性肿瘤雌孕激素受体的单克隆抗体免疫组化研究

利用抗雌激素受体（ＥＲ）和孕激素受体（ＰＲ）的两种单克隆抗体对３１例卵巢上皮性肿瘤新鲜冰冻标本进行ＡＢＣ法测定，ＥＲ、ＰＲ的阳性表达率分别为４５．２％和４８．４％，恶性肿瘤ＥＲ的含量高于良性者，ＰＲ在良、恶性肿瘤间未见有明显差异。提示：部分卵巢上皮性肿瘤属于激素依赖性肿瘤，对晚期卵巢癌可试用激素疗法。ＥＲ、ＰＲ在宫内膜样癌和浆液性癌的含量高于其它类型上皮性肿瘤，高分化者受体阳性率及含量高于低分化者；ＥＲ或ＰＲＦ阳性者预后好于阴性者，二者具独立的预后因素，且ＥＲ、ＰＲ双阳性者预后比ＥＲ阳性、ＰＲ阴性或ＥＲ阴性、ＰＲ阳性者好。     

女性生殖系统恶性肿瘤组织胞浆雌激素及孕激素受体的研究

应用葡聚糖－活性炭单点饱和分析法测定３４４例子宫内膜癌，１７７例子宫颈癌，２８９例卵巢恶性肿瘤，１０例外阴癌及４例输卵管癌组织胞浆的雌激素受体（ＥＲ）和孕激素受体（ＰＲ）含量。结果：ＬＲ及ＰＲ均量从高到低均依次为子宫内膜癌，卵巢恶性肿瘤及子宫颈癌。并探讨生殖系统不同恶性肿瘤组织胞浆ＥＲ和ＰＲ阳性率与患者绝经前后、肿瘤分化程度、临床期别及其预后之间的关系。提示：ＥＲ和ＰＲ含量对指导肿瘤患者术后内分泌治疗及判断预后有一定价值。     

雌激素受体、孕激素受体、血管内皮生长因子及其受体在子宫肌瘤中的表达和临床研究

目的:探讨子宫肌瘤的发生机制,检测子宫肌瘤组织中雌激素受体(ER)、孕激素受体(PR)和血管内皮生长因子(VEGF)及其受体(VEGFR1,VEGFR2)的阳性表达率,并探讨其临床意义.方法:应用免疫组织法(SP)测定30例子宫平滑肌瘤和相应子宫肌层组织的3种受体的表达.结果:子宫肌瘤ER阳性率为60.00%,PR阳性率为70.00%,相应子宫肌层组织ER、PR阳性率为40.00%、43.33%,两组ER和PR阳性率比较,差异有统计学意义(P＜0.05).子宫肌瘤组织中VEGF及VEGFR1、VEGFR2蛋白表达水平,无论在增殖期或分泌期,高于相应子宫肌层组织(P＜0.01);VEGFR2表达水平高于VEGFR1(P＜0.05).结论:ER、PR、VEGF均是反映子宫肌瘤的生物学行为的指标,研制ER、PR、VEGF及其受体蛋白的拮抗剂,使子宫肌瘤萎缩或凋亡,有望成为治疗子宫肌瘤新途径.     

上皮性卵巢肿瘤组织中膜型基质金属蛋白酶-1(MT1-MMP)的表达及临床意义

目的:研究膜型基质金属蛋白酶-1(MT1-MMP)在上皮性卵巢肿瘤组织中的表达及临床意义。方法:应用免疫组化EnVision法检测40例上皮性卵巢癌(A组)、20例交界性上皮性卵巢肿瘤(B组)、20例良性上皮性卵巢肿瘤(C组)和20例正常卵巢组织(D组)中MT1-MMP的表达和预后。结果:MT1-MMP在上皮性卵巢癌中的阳性率(95%)显著高于良性卵巢肿瘤(45%)和正常卵巢(35%),A组中的强阳性率(77.5%)显著高于B组(30%)、C组(10%)和D组(10%)(P<0.05);D组中未绝经者的阳性率(66.7%)显著高于绝经者(9.1%)(P<0.05);晚期上皮性卵巢癌中的强阳性率(100%)显著高于早期的强阳性率(52.6%)(P<0.05);中低分化(G2～G3级)上皮性卵巢癌中的强阳性率(86.7%)显著高于高分化(G1级)的强阳性率(50%)(P<0.05);有淋巴转移的上皮性卵巢癌中的强阳性率(94.4%)显著高于无淋巴转移组的强阳性率(63.6%)(P<0.05)。在单因素生存分析中,A组中MT1-MMP的表达与患者预后不良有关;B组中MT1-MMP表达强阳性组(++～+++)的复发率(66.7%)显著高于MT1-MMP表达阴性～弱阳性组(-～+)的复发率(7.1%)(P<0.05)。结论:MT1-MMP可能参与卵巢的正常生理功能,它的异常高表达在上皮性卵巢癌的浸润、转移和交界性上皮性卵巢肿瘤的复发中起了重要作用,MT1-MMP的表达与患者预后不良有关。     

卵巢恶性肿瘤端粒酶活性与C-myc基因mRNA表达的研究

目的　研究端粒酶活性、C -myc基因在卵巢恶性肿瘤中的表达和相互关系。方法　在卵巢恶性肿瘤、交界性肿瘤、良性肿瘤和正常卵巢组织中 ,采用PCR -ELISA方法检测端粒酶活性 ,RT -PCR方法检测C -myc基因的mRNA表达。结果　恶性卵巢肿瘤端粒酶活性值及阳性率 (91 30 % ) ,明显高于交界性卵巢肿瘤(2 0 0 0 % ,P <0 0 1 )、良性卵巢肿瘤 (7 1 3% ,P <0 0 1 )和正常卵巢 (0 0 0 % ,P <0 0 1 )。交界性卵巢肿瘤端粒酶表达率与后两者的端粒酶活性表达率也存在显著差异 (P <0 0 1 ) ;卵巢良性肿瘤与正常卵巢组织之间端粒酶活性无差别 (P >0 0 5 )。端粒酶活性值在恶性卵巢肿瘤Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期 (P <0 0 5 ) ;分化程度低者高于分化高者 (P <0 0 5 ) ;但在组织类型和组织起源上差异无显著性 (P >0 0 5 )。恶性卵巢肿瘤组织中端粒酶活性值明显高于癌旁组织 (P <0 0 5 )。端粒酶阳性率在恶性卵巢肿瘤临床分期、组织类型和组织起源上均无差异 (P >0 0 5 )。利用RT -PCR检测C -myc基因的表达 ,发现 1 2例 (5 2 1 7% )恶性卵巢肿瘤C -myc基因有mR NA表达 ,而在良性、交界性和正常卵巢组织中均未见表达。C -myc基因阳性组端粒酶活性值显著高于阴性组。结论　端粒酶活化可以作为恶性肿瘤的分子生物     

人子宫平滑肌肿瘤的雌、孕激素受体和p~(53)蛋白表达

目的：探讨子宫平滑肌瘤与雌、孕激素受体的关系；了解ｐ５３蛋白在不同组织学类型肌瘤细胞内的表达情况。方法：直接荧光组织化学法和免疫组化法。结果：子宫肌瘤雌、孕激素受体阳性率为６５．５２％，高于子宫肌壁的雌、孕激素受体３６．３６％的阳性率。两组差异有显著性（Ｐ＜０．０５）。６０例子宫平滑肌瘤ｐ５３蛋白总阳性表达率为１８．８３％，良性平滑肌瘤组、富细胞型及子宫肉瘤组ｐ５３蛋白阳性率分别为１３．３３％、１５％和４０％。肉瘤组ｐ５３蛋白阳性率明显高于良性肌瘤组，但差异无显著性。结论：雌、孕激素对子宫平滑肌瘤的发生均有一定作用。人子宫平滑肌瘤ｐ５３蛋白阳性表达率低于女性生殖道上皮源性肿瘤，而与人纤维源性肿瘤的ｐ５３蛋白阳性表达率接近。     

雌、孕激素受体表达与宫腔粘连分离术后雌孕激素治疗疗效的相关性研究

目的:研究宫腔粘连(IUA)患者子宫内膜组织中雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)的表达,探讨其与术后雌孕激素治疗疗效的关系。方法:采用免疫组化法检测55例中重度IUA患者子宫内膜组织的ER、PR表达;患者均行宫腔镜下IUA分离术,术后给予雌孕激素周期治疗。随访患者的月经改善情况,结合宫腔镜复查结果,分析PR、ER受体与预后的相关性。结果:ER、PR在腺体及间质中的表达均无显著差异(P=0.727,P=0.453);PR低表达组、高表达组患者术后雌孕激素治疗的有效率分别为63.64%和54.55%,两组比较无显著差异(P=0.503);ER低表达组、高表达组患者术后雌孕激素治疗的有效率分别为33.33%和70.27%,两组比较差异显著(P=0.018)。结论:患者子宫内膜PR的表达不能预测预后;ER表达水平与疗效呈正相关,其可能成为IUA术后雌孕激素治疗疗效的预测指标。     

芳香化酶ER PR在卵巢浆液性肿瘤中的表达及意义

目的探讨芳香化酶、雌激素(ER)、孕激素受体(PR)与卵巢浆液性肿瘤的发病机制、临床分期、分化程度的关系以及芳香化酶与ER、PR之间是否具有相关性,进而探讨其临床意义。方法对中国医科大学第一附属医院1995—2002年手术切除的卵巢浆液性乳头状囊腺癌标本36例(恶性组)、卵巢浆液性乳头状囊腺瘤20例(良性组)及非卵巢疾病患者正常卵巢组织标本10例(正常组),用多克隆抗体免疫组化链霉素抗生物素蛋白-过氧化物酶标记法检测其芳香化酶的表达,用免疫组织化学二步法检测ER、PR的表达。结果芳香化酶在恶性组的表达率明显高于正常组及良性组(P<0.05),与恶性组的临床分期和分化程度无关(P>0.05)。ER在恶性组的表达率明显高于正常组及良性组(P<0.05),与恶性组的临床分期和分化程度无关(P>0.05)。PR在正常组及良性组的表达率明显高于恶性组(P<0.05),与恶性组的临床分期和分化程度无关(P>0.05)。结论芳香化酶、ER可能参与卵巢浆液性肿瘤的发生。     

胃癌卵巢转移亲和性的临床病理研究

目的探讨胃癌卵巢转移机制。方法分别对1996年1月至2004年10月汕头大学医学院第一附属医院等单位32例胃癌卵巢转移原发灶、转移灶以及32例对照组(无卵巢转移)胃癌组织雌激素受体(ER)、孕激素受体(PR)和黏蛋白进行测定,结合临床病理资料分析。结果32例胃癌卵巢转移病例转移灶细胞分化程度明显低于原发灶(P<0.01);ER、PR组化染色、黏蛋白组化染色结果均显著高于原发灶(P<0.01)。32例胃癌卵巢转移病例原发灶和对照组胃癌在年龄、胃癌大体形态、病理组织学类型、ER、PR亲和组化染色、黏蛋白组化染色结果差异有显著性(P<0.01)。结论以“EER”为纽带的特殊的亲和性可能在胃癌卵巢转移中起到关键性作用;胃癌卵巢转移最主要的转移方式是淋巴转移(可以多种方式共存);黏蛋白显著增多是卵巢转移癌组织学分化程度下降的物质基础及其重要的临床表现。     

Steroid receptor content in human ovarian tumors: survival of patients with ovarian carcinoma related to steroid receptor content

Steroid receptors were measured in 31 malignant and 29 benign or semimalignant ovarian tumors in a prospective study. Estrogen receptors (ER) were found more often in highly differentiated malignant tumors (86%) than in poorly differentiated ones (23%). No such difference was found for progesterone receptor (PR). Receptor content was not related to clinical stage. The median survival of patients with PR+ or ER+/PR+ malignant tumors was 30 and 31.5 months, respectively, compared to 10 and 9 months for those with receptor negative tumors. This positive prognostic information could not be demonstrated for ER alone. Receptor content and distribution were similar in benign and semimalignant tumors. Measurement of hormone receptors in ovarian cancers can thus give valuable prognostic information.     

Cytosol estrogen, progestin receptors and secretory endometrium in infertile women

The serum levels of estradiol (E2), progesterone (P), FSH, PRL and cytosol estrogen and progestin receptors (EcR, PcR) contents in the endometrial tissues were analyzed in patients with inadequate secretory endometrium. The result shows that EcR and PcR are significantly lower (EcR: P less than 0.01; PcR: P less than 0.05) in these patients than those of control group. The inadequate secretory changes of endometrium correlated with insufficient EcR and PcR contents rather than with decreased levels of serum E2, P, FSH and PRL. The authors suggest that during treatment of such patients both the hormonal levels in the peripheral blood and the EcR, PcR contents in the tissue should be considered at the same time.     

The distribution and prognostic implications of steroid receptors in endometrial carcinomas

Estradiol receptors (ER) were measured in 71 and progesterone receptors (PR) in 62 primary endometrial carcinomas. ER were found in 62 (87%) and PR in 56 (90%) of the tumors. Fifty-six tumors were ER+/PR+ and 4 were ER-/PR-. The frequency of receptor positive tumors was not significantly correlated to histological grade. Highly differentiated tumors were, however, more often ER and PR rich (greater than or equal to 30 fmole/mg protein) as compared to poorly differentiated tumors. The median ER and PR values for grade I tumors were also significantly higher than for grade III tumors. No significant differences were found in the frequency of patients with ER or PR rich tumors in the different FIGO or surgical stages. The receptor status was not related to depth of myometrial infiltration. Recurrence rates and death rates were significantly higher in patients with PR poor as compared to those with PR rich tumors. This prognostic information could not be shown for ER.     

Estrogen and progesterone receptors in tumors of the human ovary

A total of 23 malignant ovarian tumors and 5 benign or tumor-like lesions of the ovary had their estrogen receptor (ER) status, and of these 15 also had their progesterone receptor (PR) status, determined. Tumors were said to be ER+ when the receptors bound >4 fmole estradiol/mg protein and PR+ when they bound >10 fmole progesterone/mg protein. Ten of twenty-two ovarian carcinomas were estrogen receptor positive (ER+) and 3 of these also contained progesterone receptors (PR+). All 6 malignant ovarian tumors occurring in premenopausal women were ER? and PR? as were the two benign tumors occurring in two premenopausal patients. It may be that premenopausal women have tumors which are more frequently ER? PR? because their higher blood hormone levels block the estrogen and progesterone binding sites in the tissues. It was not possible to show any variation from normal in the plasma hormone levels (estradiol, estrone, testosterone, progesterone, FSH). It is suggested that hormone receptor studies of malignant ovarian tumors could aid in the selection of patients suitable for therapies based on endocrine manipulation.     

Estrogen and progesterone receptors in ovarian neoplasms

The cytoplasmic receptors for 17 beta-estradiol (ER) and progesterone (PR) were measured in 39 malignant and 15 benign ovarian neoplasms. All eight endometroid carcinomas had positive ER sites, one-half contained PR. The number of ER binding sites decreased as tumor grade increased. Conversely, none of the 11 mucinous tumors contained either ER or PR receptors. One-half of the well-differentiated serous tumors had ER (57 +/- 23 fmole/mg protein) while none of the poorly differentiated tumors had measurable binding. In serous carcinomas, PR was only detected in well-differentiated lesions (447 +/- 240 fmole/mg protein). Only one of 15 benign neoplasms contained ER and PR receptors. Correlation of tumor grade and type may help to plan hormonal therapies in advanced ovarian malignancies.     

Steroid receptors in ovarian carcinoma: Immunohistochemical determination may lead to new aspects

87 nonpretreated stage III/IV ovarian common epithelial carcinomas were studied for estrogen receptor (ER) and progesterone receptor (PR) content by both immunohistochemistry (IHC) and biochemical (DCC) analysis. While the DCC assay showed tumors to be receptor-positive in 62% (ER) and 66% (PR), receptor-positive malignant epithelial cells were only detected in 38% (ER) and 31% (PR) by IHC. There was only a low correlation between the semiquantitative results of ER and PR IHC and the corresponding values of DCC receptor determination. The finding of steroid receptor-positive stromal cells without any evidence of hormone receptor-positive epithelial tumor cells offers a possible explanation for discrepant results in numerous cases with obviously "false positive" results of DCC analysis. Since the considerable heterogeneity of steroid receptor expression present in many ovarian neoplasms can only be detected by IHC, it seems to be the appropriate method of ER and PR determination. Most patients were treated by both radical cytoreductive surgery (n = 76) and a platinum-based chemotherapy (n = 79). ER was not shown to be of significant prognostic value. However, survival was significantly better in patients with PR positive tumors (IHC and DCC) on univariate analysis. Residual tumor after primary surgery was the only remaining significant prognostic factor after multivariate analysis. Further studies are needed to clarify the biological function of steroid receptor-positive stromal cells in ovarian carcinomas.     

The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors

Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being both ER+ and PR+. There was no significant relationship between receptor expression and stage, grade, or histological subtype. Thirteen percent of diploid tumors were receptor negative in contrast to 38% of aneuploid tumors (P less than 0.01). There was no significant association between ER status and ploidy, but 60% of diploid tumors were PR+ in contrast to 33% of aneuploid tumors (P less than 0.02). Eleven percent of tumors overall were both ER rich and PR rich and comprised 23% of diploid and 5% of aneuploid tumors (P less than 0.01). Receptor-negative tumors had a median S phase of 18.8% which was significantly higher than the median S phase of 12% in receptor-positive tumors (P less than 0.02). A similar analysis was also performed on specimens from 9 patients with borderline epithelial ovarian tumors and 12 with benign epithelial ovarian tumors. Up to 50% of benign and borderline epithelial tumors had measurable receptors, but all were diploid with a relatively low S phase fraction. The functional significance of steroid receptor expression in ovarian cancer is unclear, but the association with ploidy and proliferative activity particularly in patients with malignant ovarian tumors may allow better identification of prognostic subsets and aid in selection of patients for hormonal therapy.     

卵巢子宫内膜异位症恶变过程中ER、PR蛋白表达的作用

目的探讨卵巢子宫内膜异位症恶变过程中ER和PR蛋白表达的作用。方法用免疫组化二步法检测ER和PR蛋白在卵巢子宫内膜异位症癌变组(30例),卵巢子宫内膜腺上皮不典型增生组(15例)和卵巢子宫内膜异位症组(30例)的表达。结果癌变组ER、PR的表达显著低于不典型增生组(P<0.05)及内异症组(P<0.01),不典型增生组与内异症组的表达无统计学差异(P>0.05);3组内异区的ER、PR表达无统计学差异;癌变组的癌变区、移行区的ER、PR表达明显低于内异区(P<0.01),而癌变组的癌变区和移行区两者表达无差别。癌变组的癌变区、移行区的ER、PR蛋白表达有相关性(P<0.05)。结论ER、PR表达缺失可能参与了内异症的恶变过程,内异症癌变失去了对性激素的依赖性。