子宫内膜癌标志物表达及其临床意义研究北大核心CSCD

目的探讨p53、磷酸酶与张力蛋白同源物(PTEN)、p16、人类表皮生长因子受体-2(HER-2)、Ki67的表达及其与子宫内膜癌发生发展的相关性。方法采用免疫组织化学法检测上海市普陀区妇婴保健院病理科2009月1年至2015年12月确诊的50例正常子宫内膜组织、20例不典型增生子宫内膜组织及75例子宫内膜癌中p53、PTEN、p16、HER-2及Ki67的表达,并对不同子宫内膜组织的表达结果进行比较。结果 p53、PTEN、p16、HER-2和Ki67在正常子宫内膜和子宫内膜癌中的表达差异均有统计学意义(P<0.05),在不典型增生子宫内膜中HER-2和Ki67表达显著高于正常子宫内膜(P<0.05),子宫内膜癌与不典型增生子宫内膜中PTEN、Ki67的表达差异有统计学意义(P<0.05)。在Ⅰ型和Ⅱ型子宫内膜癌之间p53、PTEN、p16、HER-2表达差异有统计学意义(P<0.05),Ki67在Ⅰ型和Ⅱ型子宫内膜癌间表达相近(P>0.05)。p53在子宫内膜癌的表达率与肿瘤的分化程度、浸润深度、脉管情况及临床分期密切相关(P<0.05),而PTEN、p16、HER-2和Ki67的表达与这些临床病理特征无关(P>0.05)。结论 p53、PTEN、p16、HER-2和Ki67蛋白的表达与子宫内膜癌的发生发展相关,在实际临床工作中可用于子宫内膜病变的病理诊断。     

Skp2蛋白与子宫内膜样癌发生及临床病理特征的关系

目的探讨细胞S期激酶相关蛋白(Skp2)在子宫内膜样癌中的表达变化及其与患者临床病理特征的关系。方法选取山东省肥城矿业集团中心医院病理科2011年1月至2012年12月收集的83例子宫内膜样癌组织标本、同期收集的30例正常子宫内膜组织标本,分析Skp2蛋白表达与患者临床病理特征的关系。结果子宫内膜样癌组织中Skp2蛋白阳性表达41例,正常子宫内膜组织中Skp2蛋白阳性表达仅2例,子宫内膜样癌组织中的Skp2蛋白阳性表达率49.40%显著高于正常子宫内膜组织的6.67%(P0.05);子宫内膜样癌组织中Skp2蛋白阳性表达与患者的临床分期、分化程度、发生淋巴结转移具有显著的相关关系(P0.05)。结论 Skp2在子宫内膜样癌中表达水平显著升高,并且与患者的临床分期、分化程度、发生淋巴结转移具有密切关系。     

p27~(kip1)和p57~(kip2)在宫颈癌组织中的表达及其预后意义

目的:探讨细胞周期调控抑制因子p27~(kip1)和p57~(kip2)在宫颈癌发生发展中的作用及预后意义。方法:采用免疫组化二步法检测p27~(kip1)和p57~(kip2)在48例宫颈癌(宫颈癌组)、13例宫颈上皮内瘤变(CIN组)和15例正常宫颈组织(正常组)中的表达。结果:p27~(kip1)和p57~(kip2)在宫颈癌组中的阳性表达率分别为25·00%和20·83%,显著低于正常组和CIN组(P<0·01,P<0·01),而后两组比较差异无统计学意义(P>0·05)。p27~(kip1)表达与宫颈癌病理分化程度显著相关(P<0·01);p57~(kip2)表达与宫颈癌病理分化程度及肿瘤大小有关(P<0·05,P<0·05);两者均与临床分期、组织学类型及淋巴结转移无关(均P>0·05)。p27~(kip1)与p57~(kip2)表达呈极显著正相关(r=0·621,P<0·01)。Kaplan-Meier单因素分析宫颈癌患者生存时间与p27~(kip1)及p57~(kip2)阳性表达有关(P<0·05,P<0·01)。结论:p27~(kip1)和p57kip2的低表达或缺失可能在宫颈癌发生发展中起重要作用,可能与预后不良有关。     

子宫内膜癌中p16、E-cad mRNA表达的研究

目的 :探讨p16及E 钙粘附蛋白 (E cad)基因mRNA在子宫内膜癌中的表达及意义。方法 :采用RT PCR技术检测 3 0例子宫内膜癌及 8例正常子宫内膜组织的p16及E cadmRNA的表达。结果 :①子宫内膜癌p16mRNA的阳性表达明显低于正常子宫内膜 (P <0 .0 1) ,但p16mRNA的表达与子宫内膜癌的组织病理分级无关 ;②E cadmRNA在子宫内膜癌中呈低表达 ,正常组织内呈强阳性表达 ,二者差异非常显著 (P <0 .0 1) ,并且在子宫内膜癌中E cadmRNA的阳性表达与组织病理学分级呈负相关 (P <0 .0 5 )。结论 :p16、E cadmRNA的表达在子宫内膜癌的发生及进展过程中起重要作用     

子宫内膜癌组织中环氧化酶-2增强表达的临床意义

目的:探讨环氧化酶2(COX2)在子宫内膜癌组织中的表达,COX2与雌激素受体(ER)表达的关系及COX2在子宫内膜癌发生发展中的意义。方法:应用RTPCR技术检测30例子宫内膜癌、相应癌旁正常内膜腺体及15例子宫良性肿瘤中COX2mRNA的表达。应用免疫组化方法测定30例内膜癌中ER表达情况。结果:COX2mRNA在30例子宫内膜癌组织中有28例表达水平明显增高,癌组织与正常内膜腺体或良性肿瘤间COX2的表达差异有显著性意义(P<0.05)。ER阳性组与ER阴性组的COX2表达差异有非常显著性意义(P<0.01)。结论:子宫内膜癌组织中COX2mRNA表达水平高于正常内膜腺体或子宫良性肿瘤,激素依赖型子宫内膜癌中COX2表达高于非激素依赖型内膜癌且其表达在子宫内膜癌的发生、发展中具有重要意义。     

子宫内膜癌组织中雌激素及孕激素受体亚型的表达研究

目的探讨子宫内膜癌组织中雌激素受体(ER)亚型mRNA及孕激素受体(PR)亚型mRNA和蛋白表达水平的变化及其意义。方法采用RT-PCR法检测66例子宫内膜癌和30例正常子宫内膜组织ER、PR亚型mRNA的表达,采用蛋白印迹法检测PR亚型蛋白的表达。结果(1)ERαmRNA在子宫内膜癌和正常子宫内膜组织中的表达水平分别是8.00±7.77、3.84±2.57,而ERβmRNA的表达水平分别是4.15±3.55、0.41±0.29,子宫内膜癌组织中ERα、ERβmRNA表达水平均高于正常子宫内膜,两种组织间分别比较,差异均有统计学意义(P<0.05)。(2)PR、PRA和PRB蛋白表达及PR mRNA表达的降低与子宫内膜癌的发生有关(P<0.05),而PRA与PRB蛋白表达的比值和PRB mRNA的表达与子宫内膜癌的发生无明显相关性(P值分别为0.550、0.901)。(3)子宫内膜癌组织中PRB mRNA与ERβmRNA的表达水平呈正相关关系(r=0.43,P<0.01)。结论子宫内膜癌组织中ER亚型mRNA表达上调、PR蛋白和mRNA表达的下调可能参与了子宫内膜癌的发生;PRB mRNA与ERβmRNA表达呈正相关关系。     

PTEN蛋白在卵巢子宫内膜异位囊肿及卵巢子宫内膜样癌组织中的表达及临床意义

目的 探讨卵巢子宫内膜异位囊肿及卵巢子宫内膜样癌组织中抑癌基因PTEN蛋白表达及意义.方法 利用免疫组化SP法和蛋白质免疫印迹法检测1985-2005年中国医科大学附属第一医院妇科手术切除的卵巢子宫内膜异位囊肿30例、卵巢子宫内膜样癌标本30例和正常增生期子宫内膜20例组织中PTEN蛋白的表达.结果 PTEN蛋白主要定位于细胞浆中,在正常子宫内膜均为阳性表达,在卵巢子宫内膜异位囊肿组织中染色强度和范围较正常子宫内膜弱(0.77±0.08对1.59±0.12,P<0.05);而在卵巢子宫内膜样癌组织中表达明显下降,与正常子宫内膜和卵巢子宫内膜异位囊肿比较,差异有统计学意义(分另q为0.55±0.08对1.59±0.12,0.55±0.08对0.77±0.08,P<0.05),且与组织分化程度、临床病理分期及有无子宫内膜异位症病史有关;分期越晚,分化程度越低,蛋白表达越少.结论 PTEN蛋白失活可能是卵巢子宫内膜异位囊肿向卵巢子宫内膜样癌发生过程中的重要事件,且检测glEN蛋白表达对判断患者预后具有一定意义.     

DACH1在子宫内膜癌的表达及与ER、PR表达的相关性

目的:探讨细胞命运决定因子DACH1蛋白、ER、PR在子宫内膜癌的表达及分析其与子宫内膜癌临床病理指标及预后的关系。方法:免疫组化技术检测80例子宫内膜癌、20例正常子宫内膜、10例复杂增生子宫内膜和10例不典型增生子宫内膜组织标本中DACH1蛋白、ER、PR的表达,分析其与子宫内膜癌患者临床病理参数及预后的关系。结果:在子宫内膜癌、正常子宫内膜、不典型增生和复杂增生子宫内膜中DACH1蛋白表达的阳性率分别为36.3%(29/80)、95.0%(19/20)、8/10、10/10,DACH1蛋白在子宫内膜癌中的表达显著低于非癌组(P=0.000)。DACH1表达阳性率内膜癌Ⅰ期为47.7%,Ⅱ~Ⅳ期为22.2%,两者差异有统计学意义(P0.05)。DACH1表达阳性率与内膜癌的病理分级有关,G1~G2级显著高于G3级(43.6%vs 20.0%,P0.05)。内膜样癌中DACH1表达阳性率为42.2%,特殊类型癌中DACH1表达的阳性率为2/16,两者差异有统计学意义(P0.05)。单因素生存分析显示DACH1阳性组子宫内膜癌患者的总体生存率明显高于DACH1阴性组(P0.05)。80例子宫内膜癌组织中34例呈ER阳性表达,42例呈PR阳性表达,DACH1蛋白表达与ER蛋白表达呈正相关(ρ=0.245906,P0.05),与PR蛋白表达呈正相关(ρ=0.3527758,P0.01)。结论:DACH1蛋白在子宫内膜癌组织表达缺失,且和ER、PR表达有一定的相关性,它在子宫内膜癌的发生、发展及预后中可能起重要作用。     

eIF-4E和PDGF在子宫内膜癌中的表达及临床意义

目的:探讨子宫内膜癌组织中真核细胞翻译起始因子4E(eIF-4E)及血小板衍生生长因子(PDGF)蛋白的表达及临床意义。方法:用免疫组化法检测51例子宫内膜癌组织、35例子宫内膜癌周2 cm组织及42例正常子宫内膜组织中eIF-4E及PDGF蛋白的表达,分析其与子宫内膜癌临床病理特征的关系。结果:eIF-4E蛋白在正常子宫内膜与子宫内膜癌周组织中的表达差异无统计学意义(P0.05),其在子宫内膜癌组织中的表达明显高于正常子宫内膜组织及子宫内膜癌周组织(P0.05);eIF-4E蛋白在子宫内膜癌高中分化组和低分化组中的阳性表达差异无统计学意义(P0.05)。PDGF蛋白在正常子宫内膜与子宫内膜癌周组织中的表达差异无统计学意义(P0.05),其在子宫内膜癌中的表达明显高于正常内膜和子宫内膜癌周组织(P0.05);PDGF蛋白在子宫内膜癌低分化组的表达高于高中分化组织(P0.05)。结论:在子宫内膜癌中eIF-4E和PDGF表达增高。PDGF在低分化癌组织的表达高于高中分化癌组织,其在子宫内膜癌形成的早期阶段可能起一定作用;而eIF-4E在癌组织中呈持续表达,可能可作为一种新的肿瘤标志物。     

抑癌基因PTEN、p27与子宫内膜异位症发病的关系

目的:探讨抑癌基因PTEN、p27在子宫内膜异位症(EMs)发生、发展中的作用。方法:采用免疫组化SP法检测32例EMs患者(EMs组)在位及异位子宫内膜PTEN和p27的表达,并与20例正常内膜对照组在位内膜进行比较。结果:PTEN、p27在EMs组异位和在位内膜的表达无显著差异(P>0.05),但二者均低于对照组水平(P<0.05);PTEN、p27在EMsⅠ-Ⅱ期的表达显著高于Ⅲ-Ⅳ期(P<0.05),并与EMsr-AFS分期呈负相关(P<0.05)。各组内膜PTEN和p27的表达均呈正相关(P<0.05)。对照组PTEN、p27分泌期的表达均高于增生期(P<0.05),而EMs组在位内膜的表达均无周期性改变(P>0.05),但其分泌期的表达显著低于对照组同期水平(P<0.05)。结论:抑癌基因PTEN、p27在EMs在位和异位内膜的低表达及二者的协同作用,可能与EMs的发生发展有密切关系。     

Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium

We aimed to investigate if expressions of survivin and p27 proteins are involved in the development of endometrioid carcinoma, along with whether there are any correlations between these proteins and loss of wild-type PTEN that is found in up to 80% of endometrial carcinomas. We also studied their correlations with classical prognostic factors and survival in endometrial carcinoma. To our knowledge, this is the first time survivin expression is investigated in endometrial hyperplasia along with endometrioid adenocarcinoma. For immunohistochemical analysis, 29 endometrioid adenocarcinoma, 38 endometrial hyperplasia, and 10 proliferative endometrium tissue samples were selected in the pathology archives. Staining of cells was scored as +2 if >50%, +1 if <50%, and negative if none were stained positive. Survivin expression increased from proliferative to hyperplasia to carcinoma cases. PTEN and p27 expressions decreased in hyperplasia and carcinoma cases with respect to proliferative endometrium. All these differences were statistically significant (P < 0.05). PTEN positively correlated to p27 (P < 0.05); however, neither was correlated with survivin. None of these genes were correlated with classical prognostic factors such as grade and myometrial invasion in endometrioid adenocarcinoma. However, mean survival was statistically significantly higher in PTEN-positive cases (46.6 vs 16.4 months) (P < 0.05). Survivin overexpression might be one of the important mechanisms in the development of endometrioid adenocarcinoma along with lost or decreased activity of PTEN and p27. However, survivin seems to exert its role in ways different from those of PTEN or p27 in the development of endometrioid adenocarcinoma. These findings on the role of survivin in endometrioid adenocarcinoma should be confirmed and the pathways through which survivin acts in endometrioid adenocarcinoma studied further with a larger sample size.     

p16和CDK4在子宫内膜腺癌中的表达及其临床意义

目的 :探讨p16和细胞周期素依赖性激酶 4 (cyclindependentkinase 4 ,CDK4 )在子宫内膜腺癌中的表达及其临床意义。方法 :采用免疫组化SP法检测 32例子宫内膜腺癌中p16和CDK4蛋白的表达。结果 :32例子宫内膜腺癌中p16蛋白表达阳性率为 4 3.8% ,p16阳性表达与子宫内膜腺癌的组织学分级、肌层浸润深度和淋巴结转移呈负相关 (P <0 .0 5 ) ,但和临床分期无关 (P >0 .0 5 )。CDK4在子宫内膜腺癌中的阳性表达率为 68.8%(2 2 /32 ) ,CDK4阳性表达与子宫内膜腺癌的浸润深度和淋巴结转移呈正相关 (P<0 .0 5 ) ,与组织学分级和临床分期无关 (P >0 .0 5 )。p16和CDK4的表达呈负相关 (P <0 .0 5 )。结论 :p16和CDK4作为细胞周期调控因子可能参与了子宫内膜腺癌的发生发展     

子宫内膜癌组织中垂体肿瘤转化基因PTTG的表达及其意义

目的 检测子宫内膜癌组织中垂体肿瘤转化基因PTTG的表达,并分析其与碱性成纤维细胞生长因子(bFGF)蛋白表达和微血管密度(MVD)计数的相关性,探讨其在子宫内膜癌发生、发展中的作用。方法 采用RT-PCR技术,检测50例子宫内膜癌组织中PTTG mRNA的表达,并进行半定量分析;应用免疫组化链霉菌抗生物素蛋白-过氧化酶连接(SP)法,检测PTTG和bFGF蛋白的表达,CD34标记血管内皮细胞并计数肿瘤间质MVD;结合临床病理特征、bFGF蛋白及MVD计数进行分析。另选择15例增生性子宫内膜和12例正常子宫内膜组织作为对照。结果 子宫内膜癌组织中PTTG基因呈过度表达,内膜癌组织中PTTG mRNA的阳性表达率及平均表达水平(分别为96％,0.84±0.08)显著高于增生性子宫内膜(分别为60％,0.78±0.06)及正常子宫内膜组织(分别为33％,0.48±0.12),3组间分别比较,差异均有极显著性(P<0.01);内膜癌组织中PTTG蛋白的阳性表达率(70％)明显高于增生性子宫内膜(40％)及正常子宫内膜组织(17％),3组间分别比较,差异也均有极显著性(P<0.01);PTTG基因的表达与手术病理分期、淋巴结转移及肌层浸润有明显相关性(P<0.05),且其在子宫内膜样腺癌组织中的表达显著高于其他类型的内膜癌组织(P<0.05);PTTG基因的表达与年龄及病理分级无关(P>0.05)。子宫内膜癌组织     

Cyclic changes in the expression of p57(kip2) in human endometrium and its regulation by steroid hormones in endometrial stromal cells in vitro

We investigated the expressions of p57(kip2) and p27(kip) and its regulation by steroids in the normal and abnormal human endometrium. Endometrial p27(kip1) and p57(kip2) messenger RNA (mRNA) were markedly increased in the secretory phase. P57(kip2) protein was absent in proliferative phase but appeared in glandular epithelium together with early- to mid-secretory phase stromal cells. During the late secretory phase, strong P57(kip2) protein immunoreactivity was found in the stromal cells. In both endometrial hyperplasia and cancer, the expression of P57(kip2) protein was low. In cultured human endometrial stromal cells (ESCs), p27(kip1) mRNA levels were increased together with the decidual marker prolactin (prl), following treatment with 17β-estradiol (E2) and progesterone (P4). At 1 nmol/L, the glucocorticoid receptor (GR) agonist dexamethasone (DEX) induced prl, p57(kip2) , and p27(kip1) mRNA in ESCs. Taken together, upregulation of p57(kip2) may play an important role in the decidual differentiation by P4 and growth inhibition of malignant cells in human endometrium.     

微管相关蛋白LC3和组织蛋白酶D在子宫内膜样腺癌中的表达及意义

目的:探讨微管相关蛋白LC3、组织蛋白酶D在子宫内膜样腺癌组织中的表达及与临床病理参数之间的关系。方法:用免疫组织化学法检测12例正常增生期子宫内膜、12例子宫内膜增殖症以及51例子宫内膜样腺癌组织中LC3和组织蛋白酶D的表达并分析。结果:LC3在子宫内膜样腺癌组织的表达强度显著低于正常增生期内膜和子宫内膜增殖症(P＜0．001,P＜0．001) LC3在子宫内膜样腺癌中的表达强度与组织学分级以及手术病理分期呈明显的负相关(r=-0．390,P＜0．001;r=-0．312,P＜0．05)。组织蛋白酶D在子宫内膜样腺癌组织中的表达显著低于正常增生期内膜(P＜0．05)。结论:自噬活性相关的LC3、组织蛋白酶D在子宫内膜样腺癌中的表达下降,自噬活性的改变可能参与了子宫内膜样腺癌的发生和演进过程。     

Coexpression index of estrogen receptor alpha mRNA isoforms in simple, complex hyperplasia without atypia, complex atypical hyperplasia and adenocarcinoma

OBJECTIVE: Estrogen receptor isoforms are postulated to play an important role in modulating the estrogen response. To clarify the molecular mechanisms through which malignant changes are activated in endometrium, this study aims to examine the expression profiles of wild-type ER-alpha and their splice variants and to assess the number of coexisting mRNA isoforms of ER-alpha in normal endometrium as well as in endometrial hyperplasia and endometrial endometrioid adenocarcinoma. METHODS: Human endometrium and specimens including endometrial hyperplasia and endometrial cancer were obtained during surgery. Endometrial data were classified into four groups: simple hyperplasia (n=24), complex hyperplasia (n=15), atypical hyperplasia (n=11), endometrial endometrioid adenocarcinoma (n=19) (grade 1, grade 2 morphological degree) and proliferative endometrium (n=24) as a control group. Total cellular RNA was extracted from endometrial tissues using Total RNA Prep Plus. A real-time quantitative RT-PCR assay was developed to quantify the wild-type ER-alpha and ER-alpha mRNA isoforms copy numbers. We have evaluated the variation in ERs mRNA level between normal endometrium and endometrial hyperplasia and adenocarcinoma. We also evaluated the "sharing indicator". It is a factor of mRNA ER-alpha holding shares in whole mRNA it assume quotient of ER-alpha slicing variant to all variants of mRNA ER-alpha. RESULTS: It was found that the number of coexisting mRNA isoforms was significantly higher in adenocarcinoma endometrium than that evaluated for various degrees of hyperplasia endometrium and normal proliferative endometrium (p<0.05, the Kruskal-Wallis test). CONCLUSION: The risk for progression of endometrial hyperplasia to atypical hyperplasia and eventually endometrioid adenocarcinoma may be accompanied by an increase in the number of alternative splicing variants of mRNA ER-alpha.     

Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma

OBJECTIVE: The expression of claudins, the main tight junction proteins involved in cell adhesion and carcinogenesis, was studied in endometrioid (type I) and seropapillary (type II) endometrial adenocarcinoma. The characteristics and possible diagnostic potential of claudin expression pattern were investigated in the two cancer types having different prognosis. METHODS: Protein and mRNA expression of claudins was evaluated in 17 endometrioid carcinomas and 15 seropapillary adenocarcinomas by immunohistochemistry and real-time PCR in comparison with 38 cases of hyperplasia, normal proliferative and secretory endometrium samples. Further, protein expressions used in diagnostics (estrogen and progesterone receptors, p53, PCNA and beta-catenin) were also studied. RESULTS: In endometrioid carcinoma and hyperplasia low claudin 1 and high claudin 2 protein contents, whereas in seropapillary adenocarcinoma high claudin 1 and low claudin 2 levels were detected. Intense protein expression was noted for claudins 3, 4, 5, and 7, without significantly different patterns in carcinoma, hyperplasia, secretory, and proliferative endometrium. Real-time PCR results confirmed differences in claudin 1 but not claudin 2 mRNA expression, whereas some minor discrepancies were observed in comparison with immunohistochemistry patterns. CONCLUSION: The two types of endometrial adenocarcinomas were well distinguished by claudins 1 and 2 by immunohistochemistry, claudins 3, 4, and 7, however, did not prove useful in distinguishing the two entities. The similar claudin pattern seen in hyperplasia and endometrioid carcinoma and the differences regarding seropapillary adenocarcinoma support the dualistic model of endometrial carcinogenesis. The claudin pattern of the two tumor types might reflect a different cellular or pathogenetic pathway as well as a different cell adhesion behavior explaining the invasive properties.     

HIF1α、Glut1在子宫内膜癌中的表达及其临床意义

目的:探讨HIF1α、G lut1在子宫内膜癌中的表达及其临床意义,并分析两者的相关性。方法:用免疫组化S-P法检测15例正常子宫内膜、17例不典型增生子宫内膜、45例子宫内膜癌组织中HIF1α、G lut1的表达。结果:HIF1α、G lut1在子宫内膜癌和不典型增生子宫内膜中的阳性率明显高于正常子宫内膜,差异有统计学意义(P<0.05)。在子宫内膜癌组织中HIF1α蛋白阳性表达率与组织病理学分级、手术病理分期无关(P>0.05),但与肌层浸润深度和淋巴结转移有关,差异有统计学意义(P<0.05);G lut1随病理组织学分级的增加、手术病理分期的进展、肌层浸润深度的加深和淋巴结转移,其阳性率逐渐上升,差异有统计学意义(P<0.05);HIF1α蛋白、G lut1蛋白表达呈正相关(r=0.741,P=0.000)。结论:HIF1α、G lut1蛋白的异常表达与子宫内膜癌的发生、发展有一定的关系。     

子宫内膜增生过长和子宫内膜样腺癌中VEGF 和TSP-1表达与血管新生研究

目的探讨子宫内膜增生过长及子宫内膜样腺癌中血管内皮生长因子(VEGF)和血小板反应素1(TSP-1)表达与血管新生的关系以及对子宫内膜样腺癌的发生、发展中的作用.方法采用免疫组织化学方法分别检测子宫内膜正常(12例)、增生过长(13例)、不典型增生(18例)及子宫内膜样腺癌(50例)中微血管密度(MVD)、VEGF及TSP-1表达情况.结果子宫内膜不典型增生和内膜样腺癌中MVD明显大于内膜正常及增生过长者(P＜0.05),子宫内膜样腺癌IA期与不典型增生二者的MVD差异无显著性(P＞0.05),而与正常内膜和增生过长者差异有显著性(P＜0.05);VEGF表达与上述不同内膜病变中MVD呈正相关(r=0.843,P=0.000 1),而TSP-1表达仅在子宫内膜样腺癌中分别与MVD和VEGF呈负相关趋势(r=-0.233,P=0.1041;r=-0.235,P=0.100 3);在子宫内膜样腺癌中TSP-1间质高表达且具有异质性.结论子宫内膜不典型增生和子宫内膜样腺癌中VEGF对血管新生起正向调节作用;TSP-1在部分腺癌患者中表达增强,但其负向调节作用较弱,可能会使血管新生开关平衡失调,与子宫内膜样腺癌发生及发展有关.     

The expression of Cdk inhibitors p27kip1 and p57kip2 in mouse placenta and human choriocarcinoma JEG-3 cells

This study was to investigate the expression of Cdk inhibitors p27kip1 and p57kip2 during the development of mouse placenta and during the steroid-treated culture of human choriocarcinoma JEG-3 cells. The p27kip1 mRNA in mouse placenta was highly expressed in 18 days p.c. than that in other groups. But, p57kip2 mRNA expression was high in 12, 14, and 16 days p.c., then decreased in 18 days p.c. The p27kip1 protein expression pattern was similar to mRNA. But, p57kip2 expression was higher in 14 days p.c. than that in other groups. The p27kip1 protein in mouse placenta was gradually increased in labyrinth zone from 12 days to 18 days p.c. However, p57kip2 protein was slightly decreased in labyrinth zone from 12 days to 18 days p.c. These reverse patterns of p27kip1 and p57kip2 expression were also shown in decidua and spongiotrophoblast. The p27kip1 mRNA expression was very low in human choriocarcinoma JEG-3 cells with estradiol concentration-independent manner. In 5 and 50 ng DEX-treated groups, p27kip1 mRNA was dramatically increased in comparison with control groups. The p57kip2 mRNA was not detected in JEG-3 cells. This result shows that p27kip1 may play a role in late period of mouse placental development and p57kip2 may play a role in middle period of mouse placental development, and that p27kip1 may play a role in growth inhibition of human choriocarcinoma cells and could be up-regulated by DEX in human choriocarcinoma.