GPER在子宫内膜样腺癌中的表达及其与ER的相关性

目的:研究GPER(G protein-coupled estrogen receptor)在子宫内膜样腺癌(EEC)组织中的表达情况,探讨GPER对EEC临床病理因素、预后的意义及其与雌激素受体(ER)之间的相关性。方法:采用实时定量PCR技术检测EEC组织中的GPER mRNA含量,免疫组化法检测GPER蛋白含量,分析GPER表达对EEC的临床意义。结果:GPER高表达于FIGO晚期、低分化、子宫肌层深浸润及淋巴转移的EEC组织中。单因素分析结果显示,GPER mRNA高表达的患者预后较差(OS,P=0.001;DSS,P=0.001;PFS,P0.001),GPER蛋白阳性的患者预后亦较差(OS,P=0.009;DSS,P=0.009;PFS,P0.001)。多因素分析发现,GPER不是影响EEC患者预后的独立因子。GPER与ER无统计学相关性。结论:GPER不是EEC预后的独立因子,但在其临床生物学行为中扮演重要的角色。     

肾上腺髓质素与妇科肿瘤的研究进展

肾上腺髓质素(ADM)在许多肿瘤细胞系和恶性组织中均有表达.ADM可以促进细胞增殖,抑制细胞凋亡,诱导肿瘤血管生成,帮助肿瘤细胞逃避免疫监视,从而在肿瘤的发生发展中起重要作用.综述ADM在妇科肿瘤中的研究情况,旨在为妇科肿瘤的早期诊断、治疗和判断预后提供新线索.     

Toll样受体与子宫内膜及子宫内膜异位症

子宫内膜异位症(EMs)发病机制尚未完全阐明.大量研究表明,免疫因素在EMs的发病机制中起重要作用.EMs免疫应答异常主要是巨噬细胞数量和活性增加及其分泌产物,如生长因子、细胞因子和血管生成因子的改变.Toll样受体(TLRs)识别特异性的病原体相关分子模式,启动和介导免疫应答,在固有免疫中发挥重要作用,并诱导产生适应性免疫反应.TLRs在正常子宫内膜中的生理作用以及在EMs中的相关研究已逐步开展,对其深人认识和研究将为EMs诊断、治疗和预后判断提供新思路和手段.     

Toll样受体与子宫内膜及子宫内膜异位症

子宫内膜异位症（EMs）发病机制尚未完全阐明。大量研究表明,免疫因素在EMs的发病机制中起重要作用。EMs免疫应答异常主要是巨噬细胞数量和活性增加及其分泌产物,如生长因子、细胞因子和血管生成因子的改变。Toll样受体（TLRs）识别特异性的病原体相关分子模式,启动和介导免疫应答,在固有免疫中发挥重要作用,并诱导产生适应性免疫反应。TLRs在正常子宫内膜中的生理作用以及在EMs中的相关研究已逐步开展,对其深入认识和研究将为EMs诊断、治疗和预后判断提供新思路和手段。     

肾上腺髓质素与妊娠关系研究进展

随着对肾上腺髓质素(ADM)生物学特性认识的深入,已发现体内多数组织器官都可以合成并分泌ADM,ADM具有多种生物学效应,并通过其受体与降钙素基因相关肽(CGRP)受体发挥生物学作用.妊娠期胎盘、绒毛膜、蜕膜和羊膜等组织都可以合成并分泌ADM,且发现该激素在正常妊娠以及病理妊娠时如流产、早产、妊娠期高血压疾病、妊娠合并糖尿病、胎儿生长受限中发挥着重要作用.进一步探讨在这些疾病中ADM的确切作用机制及其途径,并从临床与治疗的角度提出新的研究思路.     

肾上腺髓质素与妊娠关系研究进展

随着对肾上腺髓质素(ADM)生物学特性认识的深入,已发现体内多数组织器官都可以合成并分泌ADM,ADM具有多种生物学效应,并通过其受体与降钙素基因相关肽(CGRP)受体发挥生物学作用。妊娠期胎盘、绒毛膜、蜕膜和羊膜等组织都可以合成并分泌ADM,且发现该激素在正常妊娠以及病理妊娠时如流产、早产、妊娠期高血压疾病、妊娠合并糖尿病、胎儿生长受限中发挥着重要作用。进一步探讨在这些疾病中ADM的确切作用机制及其途径,并从临床与治疗的角度提出新的研究思路。     

子宫内膜样腺癌与正常子宫内膜中端粒酶hTERT mRNA和端粒酶活性的定量分析

端粒酶表达是癌症细胞逃逸正常细胞衰老的主要机制,对其研究已经成为肿瘤判断预后和诊断性标志物的重要课题。功能件端粒酶全酶由端粒酶RNA(hTR)和催化蛋白亚基(hTERT)组成,前者作为端粒DNA合成的模板引物。hTERTmRNA的表达与端粒酶酶活性的水平呈平行关系,提示诱导hTERT基因表达可调节端粒酶活性。为验证定量测定hTERT     

肾上腺髓质素在人类妊娠中的作用研究进展

肾上腺髓质素(adrenomedullin,AM)自1993年发现后受到广泛关注,肾上腺髓质素在全身多个系统中均发挥重要作用,主要作用为扩张血管、调节体内水钠代谢、影响细胞增殖和凋亡、抗肿瘤细胞凋亡、促进肿瘤血管生成等,大量研究表明,肾上腺髓质素及其受体在女性生殖内分泌系统中有表达,并且肾上腺髓质素在正常妊娠的胎盘、子宫、母血和脐血中水平增高,并凡发现肾上腺髓质素参与子痫前期、妊娠期糖尿病、胎儿生长受限等病理性妊娠过程,提示肾上腺髓质素在妊娠过程中的作用具有多效性.就肾上腺髓质素及其受体在妊娠中的作用综述.     

肾上腺髓质素在人类妊娠中的作用研究进展

肾上腺髓质素（adrenomedullin,AM）自1993年发现后受到广泛关注,肾上腺髓质素在全身多个系统中均发挥重要作用,主要作用为扩张血管、调节体内水钠代谢、影响细胞增殖和凋亡、抗肿瘤细胞凋亡、促进肿瘤血管生成等,大量研究表明,肾上腺髓质素及其受体在女性生殖内分泌系统中有表达．并且肾上腺髓质素在正常妊娠的胎盘、子宫、母血和脐血中水平增高,并且发现肾上腺髓质素参与子痫前期、妊娠期糖尿病、胎儿生长受限等病理性妊娠过程,提示肾上腺髓质素在妊娠过程中的作用具有多效性。就肾上腺髓质素及其受体在妊娠中的作用综述。     

经量过多患者子宫内膜中ADM表达及意义

目的:研究经量过多妇女子宫内膜中肾上腺髓质素(ADM)及其相关受体降钙素受体相关受体(CRLR)表达的变化,探讨其与疾病发生、发展的关系。方法:通过免疫组化、半定量RT-PCR及实时荧光定量RT-PCR等方法,研究经量过多组患者(n=18)与健康对照组妇女(n=22)ADM、CRLR在子宫内膜中蛋白表达和基因表达量的差异。结果:两组内膜中ADM蛋白表达出现在内膜的各细胞中,经量过多组子宫内膜间质细胞中ADM蛋白表达明显低于正常对照组(P0.05);CRLR蛋白在内膜腺上皮细胞中表达明显高于对照组(P=0.008);经量过多组内膜中血管密度值为1.12(0.8～2.2),明显低于正常组的2.3(0.6～3.6)(P0.05);经量过多组ADMmRNA比正常对照组低25.6%,而两组CRLR mRNA无明显差异。结论:ADM及其受体CRLR在正常子宫内膜生成、修复中发挥重要作用,其影响更多的作用于内膜血管生成;经量过多患者低调控ADMmRNA导致内膜中ADM蛋白表达降低,进一步影响内膜中血管生成和修复,是造成患者出血的原因之一。     

Relationship between peritoneal cytology and prognosis in endometrial carcinomas

From 1971 to 1985, peritoneal cytologic examination was performed at the time of operation in 235 previously untreated patients with endometrial carcinoma. The relationship between the cytologic findings and prognoses by stage was investigated. The results were as follows: 1. In the peritoneal cytologic examination, 44 (18.7%) out of 235 cases were positive for cancer cells in all stages, 25 (14.5%) out of 173 cases in stage I, 7 (21.2%) out of 33 cases in stage II, and 8 (32.0%) out of 25 cases in stage III. 2. Among the 20 cases of stage I endometrial carcinoma that had no macroscopic metastasis and had positive peritoneal cytologic findings for cancer cells, 5- and 10-year cumulative survival rates were 94.7 and 94.7%, against 92.7% and 90.9% in cases with negative peritoneal cytology respectively. The recurrence rate in the same stage was 12.0% for positive cases, against 9.5% for negative cases. No significant differences between positive and negative cases were found. 3. In stages II and III, the difference between the survival rates for 9 cases which have positive peritoneal cytology without macroscopic peritoneal metastasis and 47 cases with negative peritoneal cytology were not statistically significant. 4. In endometrial carcinoma without macroscopic peritoneal metastasis, the appearance of cancer cells in peritoneal cytologic examination is not correlated with the prognosis.     

Histologic control of biochemical steroid receptor analysis in endometrial carcinomas

Histologic review of 422 specimens from endometrial carcinoma submitted for biochemical cytosol estrogen and progesterone receptor analysis revealed that 16 (4.0%) contained no evidence of carcinoma on permanent histologic sections. An additional 11 (2.5%) contained focal carcinomas on permanent sections but had no evidence of malignancy in frozen sections of the tissue submitted for receptor analyses. Despite the paucity or even absence of malignancy, many of these specimens had significant cytoplasmic estrogen and progesterone receptors derived from endometrial and myometrial tissues. Rigorous histologic control of specimens from endometrial carcinomas submitted for biochemical steroid receptor analyses is necessary to establish valid clinical and histologic associations of steroid receptor content.     

Histologic composition of endometrial carcinomas analyzed for steroid receptor content

One hundred endometrial carcinoma specimens were analyzed for estrogen receptor content and histologic composition. Benign tissue elements were identified in the majority of tissue sections. Histologic control of endometrial carcinoma specimens submitted for steroid receptor analysis is critical, because biochemical assays of whole tissue homogenates cannot determine receptor localization among tissue components.     

层粘连蛋白受体基因表达与子宫内膜癌的关系

目的 探讨67ku层粘连蛋白受体(67LR)基因表达与子宫内膜癌的关系。方法 应用免疫组化SABC法检测1990～2001年收治的44例子宫内膜癌、15例子宫内膜增殖症、47例正常子宫内膜组织中67LR的表达;采用荧光定量逆转录聚合酶链反应(FQ-RT-PCR)方法定量检测2000～2001年收治的24例子宫内膜癌、16例子宫内膜增殖症、29例正常子宫内膜新鲜组织67LRmRNA水平。结果 67LR在子宫内膜癌、子宫内膜增殖症的表达较正常子宫内膜均明显增高(P<0.001),但前两组的表达差异无显著性(P>0.05)。高、中分化子宫内膜腺癌67LR表达较低分化者为高(P<0.05);但高、中、低分化组病例67LR mRNA水平差异无显著性(P>0.05)。67LR mRNA水平与免疫组化蛋白表达无明显相关(P>0.05)。结论 67LR蛋白过度表达可能与子宫内膜癌的发生、发展有关。67LR mRNA水平与蛋白表达水平无相关。     

子宫内膜癌中Maspin的表达及其与雌激素受体表达的相关性研究

目的:检测Maspin蛋白在正常子宫内膜、不典型增生及内膜癌组织中的表达,及其与雌激素受体(ER)表达的关系,探讨Maspin在子宫内膜癌发生中的作用及其作用机制。方法:免疫组化SP法检测40例子宫内膜腺癌、18例不典型增生及10例正常子宫内膜(对照组)中Maspin蛋白的表达及其与子宫内膜癌患者临床病理特征和ER蛋白表达的关系。结果:Maspin阳性表达在正常子宫内膜组最高(9/10,90%),高于内膜不典型增生组(10/18,55.6%)和内膜癌组(17/40,42.5%),差异有统计学意义(P<0.05),在内膜癌中FIGOⅠ期的表达(13/20,65.0%)明显高于Ⅱ~Ⅲ期(4/20,20.0%;P<0.05),无淋巴结转移者(17/34,50.0%)明显高于有淋巴结转移者(0/6;P=0.030),但与组织学分级及肌层浸润程度无关(P>0.05)。ER在正常子宫内膜、内膜不典型增生及内膜癌组织的阳性表达率分别为(10/10,100.0%)、(13/18,72.2%)和(20/40,50.0%),各组间差异有统计学意义(P<0.05);内膜癌组织中FIGOⅠ期的表达(14/20,70.0%)明显高于Ⅱ~Ⅲ期(6/20,30.0%;P<0.05);内膜癌高、中、低分化组中ER表达率分别为(11/15,73.3%)、(8/18,44.4%)、(1/7,14.3%),组间差异有统计学意义(P<0.05);无淋巴结转移者(20/34,58.8%)明显高于有淋巴结转移者(0/6;P=0.020),肌层浸润≤1/2者(16/24,66.7%)明显高于肌层浸润>1/2者(4/16,25.0%;P<0.05)。子宫内膜癌中,Maspin的表达与ER的表达存在正相关关系(r=0.394,P<0.05)。结论:从正常子宫内膜、内膜不典型增生到内膜癌,Maspin蛋白表达逐渐降低,且其低表达与子宫内膜癌临床分期晚、淋巴结转移有关,并与ER蛋白表达呈一致性,提示Maspin蛋白的表达可能受雌激素调控,参与了子宫内膜癌发生发展和转移过程。     

Genetic alterations in endometrial carcinomas

Van Nostrand K, Johnson G, Monk, B, Wilczynski S, Chapman J, Brightman K, Schell M, Berman M, Manetta A, DiSaia P, Fan H. Genetic alterations in endometrial carcinomas. Int J Gynecol Cancer 1998; 8 : 415–422.
Endometrial cancer is the most common gynecologic malignancy. Grade, lymph node status, and stage are known prognostic indicators and yet it is difficult to predict those patients at high risk for recurrence. To evaluate the prognostic value of a variety of oncogenes (K- ras , Her-2/ neu , c- myc ) and of p53 mutations, we studied 49 endometrial cancers using Southern blots, PCR/SSCP analysis, and PCR direct sequencing. Chart review was performed to obtain clinical information (pathology, survival statistics). Statistical analysis was performed using log-rank, chi-square, and life table analysis. The mean age of the patients was 66 years. Overall, 26 tumors (53%) showed some form of oncogene alteration. Patients with alterations had a higher mean age (67) than those without (60). Patients with c- myc amplification (24%) had higher grade tumors and poorer 5-year survival (58%), although not significant statistically. Twenty-four percent of patients had p53 mutations, higher stage tumors, and poorer 5-year survival (54%). K- ras (6%) and HER-2/ neu (8%) alterations were associated with lower grade tumors and were not found to be prognostic indicators. Five patients had > 1 alteration. C- myc was found less frequently associated with other alterations than expected while HER-2/ neu was found more frequently than expected. These results suggest that only 50% of endometrial cancers contain an alteration of these genes and that other alterations may exist and await identification. C- myc amplification and p53 mutations appear to be present in those patients with poorer prognosis; screening for these alterations may be useful in predicting those with a high risk for recurrence, thus allowing early adjuvant therapy.     

Association of immunohistochemical profiles with histotypes in endometrial carcinomas

ObjectiveAlthough a large number of endometrial cancer patients are cured with surgery alone, there are significant numbers of patients with more aggressive variants of endometrial carcinoma for whom the prognosis remains poor. We investigated the effects of prevalence, histotypes, and immunohistochemical profiles on prognostic value in a hospital-based population.Materials and methodsA retrospective study of surgically resected primary endometrial carcinoma was included. Immunohistochemical stains were performed on formalin-fixed paraffin-embedded tissue microarray sections for β-Catenin, estrogen receptor (ER), progesterone receptor (PR), HER-2, MLH1, MSH2, MSH6, PMS2, and p53.ResultsLoss of mismatch repair expression was detected in 25.4% of samples (29/114, mean age 57 years) of the tumors. The following loss of expression was observed in patients: MLH1/PMS2 in 16.6% of patients, MSH6 in 7.0% of patients, MLH1 in 0.9% of patients, and MSH6/PMS2/MLH1 in 0.9% of patients. Immunohistochemistry of p53 was analyzed for 111 patients. A total of 13 patients (11.7%, mean age 64 years) had p53-abnormal expression (absent, cytoplasmic or diffuse strong positive patterns), and more than half (9/13, 69.2%) had endometrioid histotype. Abnormalities in p53 were significantly associated with histotype (p = 0.001), advanced tumor stage (p = 0.038), death of disease (p = 0.002), PR percentage (p = 0.002), and HER-2 expression (p = 0.018). Immunohistochemical nuclear localization of β-Catenin was detected in 7.1% of the cohort. The combination of p53 and nuclear β-Catenin expressions was not significantly predictive of disease-free or overall survival.ConclusionThe results of this study are useful for management of endometrial cancer in patients with DNA mismatch repair, abnormal p53 expression, or nuclear localization of β-Catenin.