PTEN与VEGF165 基因mRNA在卵巢癌中表达及相关性研究

目的探讨PTEN和VEGF165 基因mRNA表达在卵巢癌发生和演进中的作用.方法利用RT-PCR方法检测正常卵巢(n=5)、卵巢囊肿(n=5)、卵巢交界性肿瘤(n=9)、上皮性卵巢癌(n=60)和卵巢癌细胞系CAOV-3中PTEN和VEGF 165 基因mRNA表达.结果PTEN基因mRNA在卵巢交界性肿瘤和卵巢癌中的表达水平低于正常卵巢和卵巢囊肿,P<0.05,与卵巢癌的临床病理分期呈负相关,P<0. 05,而与组织分化程度呈正相关,P<0.05.在卵巢内膜样癌中PTEN基因mRNA表达水平显著低于浆液性或黏液性卵巢囊腺癌,P<0.05.VEGF165 基因mRNA在卵巢癌中的表达水平高于正常卵巢和卵巢囊肿,P<0.05,与卵巢癌的临床病理分期呈正相关,P<0. 05,而与组织分化程度呈负相关,P<0.05;浆液性卵巢癌中VEGF165 基因mRNA 表达水平显著高于其他上皮性卵巢癌,P<0.05.VEGF165 基因mRNA随PTEN基因mRNA表达的降低而升高,r=0.728,P<0.05.结论在卵巢癌中PTEN基因mRNA表达下调和VEGF165 基因mRNA表达上调,2个指标分别与卵巢内膜样癌和浆液性囊腺癌的发生和病理生物学行为关系密切;PTEN基因mRNA表达降低原因可能为通过上调VEGF基因mRNA表达促进新生血管形成,进而参与卵巢癌的发生和演进.     

MMP-2与VEGF165基因mRNA在卵巢癌中表达及相关性研究

目的:探讨MMP-2和VEGF165基因mRNA表达在卵巢癌发生和演进中的作用.方法:利用RT-PCR方法检测正常卵巢(n=5)、卵巢囊肿(n=5)、卵巢交界性肿瘤(n=9) 和上皮性卵巢癌(n=60)中MMP-2和VEGF165基因mRNA表达.结果:MMP-2和VEGF165基因mRNA在卵巢交界性肿瘤和卵巢癌中的表达水平高于正常卵巢和卵巢囊肿(P<0.05),与卵巢癌的临床病理分期呈正相关(P<0.05),而与组织分化程度呈负相关(P<0.05);浆液性卵巢癌中MMP-2和VEGF165基因mRNA表达水平显著高于其他上皮性卵巢癌(P<0.05).结论:在卵巢癌中MMP-2和VEGF165基因mRNA表达上调,与卵巢癌的发生和病理生物学行为关系密切;MMP-2和VEGF165基因mRNA表达上调参与了卵巢癌的发生,提高了卵巢癌的侵袭转移能力,因此,构成了卵巢癌发生和侵袭的分子基础.     

B7-H4在上皮性卵巢癌中的表达及意义

目的 探讨上皮性卵巢癌组织中B7-H4的表达及其与临床病理特征和预后的关系。方法采用免疫组化法检测66例上皮性卵巢癌、5例交界性卵巢肿瘤、8例良性卵巢肿瘤组织和20例正常卵巢组织蜡块中B7-H4的表达,分析其表达与上皮性卵巢癌临床病理特征和预后的关系。结果 B7-H4在上皮性卵巢癌组织中的阳性表达率为86.4％,在卵巢交界性肿瘤、卵巢良性肿瘤及正常卵巢组织中均不表达。B7-H4在浆液性囊腺癌、子宫内膜样癌和透明细胞癌中的阳性表达率分别为100.0％、90.0％和87.5％,均高于其在黏液性囊腺癌中的50.0％,差异有统计学意义（P＜0.05）。上皮性卵巢癌中B7-H4的表达与年龄、腹水细胞学无关,而与临床FIGO分期、组织学分级、淋巴结转移有关。B7-H4的表达与上皮性卵巢癌患者的生存情况无关（P＞0.05）。结论 B7-H4蛋白在上皮性卵巢癌组织中的表达上调,其表达与上皮性卵巢癌的发生、发展有关。     

PKP4在卵巢上皮性浆液性囊腺癌组织中的表达及其临床意义

目的:检测PKP4（plakophilin 4,又称p0071）在卵巢上皮性浆液性囊腺癌组织中的表达,探讨PKP4参与肿瘤发生发展的机制及其临床意义。方法:利用免疫组化SP法检测PKP4在55例卵巢上皮性浆液性囊腺癌,12例卵巢上皮性交界性肿瘤,13例卵巢上皮性良性肿瘤,15例正常卵巢组织中表达情况,分析其与卵巢上皮性浆液性囊腺癌患者临床病理参数及预后的关系。结果:PKP4以细胞膜、细胞质着色为主,PKP4在卵巢上皮性浆液性囊腺癌组织中阳性表达率(94.55%)明显高于正常卵巢组织(26.67%)、卵巢上皮性良性肿瘤组织(46.15%)及卵巢上皮性交界性肿瘤(75.00%)(P＜0.05)。PKP4表达随FIGO分期增加而增高(P＜0.05),是影响卵巢上皮性浆液性囊腺癌患者总生存时间和预后的独立危险因素。结论:PKP4与卵巢癌的发生、发展和预后相关,有望在卵巢癌的早期诊断及预后评估方面发挥重大意义。     

卵巢癌组织中Vasohibin基因表达与启动子区域甲基化的关系

目的探讨卵巢上皮性肿瘤中Vaso-hibin基因mRNA表达与临床特征及其启动子甲基化的关系。方法用RT-PCR检测10例良性卵巢上皮性肿瘤、8例交界性卵巢上皮性肿瘤及30例卵巢癌组织中VasohibinmRNA表达;用甲基化特异聚合酶链反应方法(MSP)检测Vasohibin启动子甲基化。结果各组标本中都有VasohibinmRNA表达,3组Vasohib-in表达的相对值良性卵巢上皮性肿瘤为0.65±0.11,交界性卵巢上皮性肿瘤为0.47±0.13,卵巢癌为0.34±0.14。卵巢癌组织中Vasohibin的表达量较交界性卵巢上皮性肿瘤组织显著降低,t=2.479,P=0.029;交界性卵巢上皮性肿瘤组织的表达量较良性卵巢上皮性肿瘤显著下降,t=3.198,P=0.006。在卵巢癌组织中,Vasohibin的表达与不同临床分期、不同分化程度以及有无淋巴结转移无关。良性卵巢上皮性肿瘤中未发现Vasohibin基因启动子甲基化;交界性卵巢上皮性肿瘤中2例发生启动子甲基化,卵巢癌中11例发生启动子甲基化,甲基化率36.7%。卵巢癌中启动子甲基化组织较未甲基化组织VasohibinmRNA表达显著降低,t=4.671,P=0.000。结论Vasohibin与卵巢癌发生存在明显相关性。Vasohibin启动子甲基化与其mRNA表达抑制密切相关,可能是Vasohibin在卵巢癌中低表达的最主要因素之一。     

上皮性卵巢癌组织中p21WAF1表达及其与P53和PCNA的相关性

背景与目的:近年研究表明,p21WAF1下调与多种肿瘤发生、发展有关,但其与上皮性卵巢癌的关系研究甚少,本研究从mRNA和蛋白水平探讨p21WAF1基因在上皮性卵巢癌发生发展中的作用及其与P53和PCNA蛋白表达的相关性.方法:应用RT-PCR法检测55例上皮性卵巢癌、32例良性卵巢肿瘤和30例正常卵巢组织中p21WAF1 mRNA表达,免疫组化法检测P21WAF1、P53、PCNA蛋白表达,并结合其临床病理参数及预后进行分析.结果:上皮性卵巢癌、良性卵巢肿瘤、正常卵巢组织中p21WAF1 mRNA阳性率分别为40.00%、56.25%、73.33%(P=0.012),P21WAF1蛋白阳性率分别为36.36%、56.25%、80.00%(P=0.001).上皮性卵巢癌p21WAF1 mRNA及其蛋白表达均低于其它两组,而P53、PCNA蛋白表达阳性率显著高于其它两组(P＜0.05).上皮性卵巢癌中p21WAF1 mRNA表达与其蛋白表达呈显著性正相关,与PCNA表达呈负相关,与P53表达无显著性相关.P21WAF1蛋白表达与PCNA、P53表达均呈负相关.P21WAF1蛋白低表达与卵巢癌FIGO分期晚有显著性相关(P=0.032),与患者年龄、组织学类型、病理分级、残余肿瘤大小无显著性相关(P＞0.05),而p21WAF1 mRNA与上述各项临床病理参数均无显著性相关(P＞0.05).单因素分析显示p21WAF1 mRNA与P21WAF1蛋白低表达患者预后差(P＜0.05).结论:上皮性卵巢癌组织中P21WAF1表达下调.p21WAF1基因检测结果有可能作为预测上皮性卵巢癌预后的一种参考指标.     

人PTPRK基因在上皮性卵巢肿瘤中的表达及其意义

目的探讨受体型蛋白酪氨酸磷酸酶(PTPRK)基因在良性、交界性和恶性上皮性卵巢肿瘤及正常卵巢上皮组织中的表达规律及其与卵巢癌的关系.方法应用免疫组化间接法检测50例卵巢癌、13例良性上皮性卵巢肿瘤、14例交界性上皮性卵巢肿瘤及10例正常卵巢上皮组织中PTPRK基因的表达,采用Kaplan-Meier生存分析比较卵巢癌患者PTPRK蛋白表达与五年生存率的关系.结果(1)良性、交界性上皮性卵巢肿瘤和卵巢癌组中,PTPRK基因的阳性表达率分别为53.9%、57.1%、18.0%,显著低于正常卵巢上皮组的表达率100%(P均＜0.001).卵巢癌组中PTPRK基因的阳性表达率显著低于良性上皮性卵巢肿瘤组(P＜0.001)和交界性上皮性卵巢肿瘤组(P＜0.01).(2)卵巢癌高分化组中PTPRK基因的表达率为62.5%,显著高于中分化组(18.8%)和低分化组(6.3%)(P＜0.01).卵巢癌淋巴结无转移组PTPRK基因的表达率为27.3%,显著高于无阳性表达的淋巴结有转移组(P＜0.05).(3)PTPRK基因表达阳性组与表达阴性组的5年生存率分别为66.7%、46.7%,两组比较,差异无显著性(P＞0.05).结论PTPRK基因表达缺失发生在上皮性卵巢肿瘤组织中,肿瘤分化程度越低或者淋巴结已有转移则该基因表达缺失越明显.PTPRK基因可能是一种肿瘤抑制基因,其不同程度的表达缺失与上皮性卵巢肿瘤的发生和发展有关.     

Survivin和基质金属蛋白酶-9基因在卵巢癌中的表达及其临床意义

目的 探讨基质金属蛋白酶(MMP)-9、凋亡抑制基因Survivin与卵巢癌局部侵袭、发生、发展的关系.方法 收集正常上皮来源卵巢组织(n=20)、良性上皮性卵巢囊肿(n=30)、卵巢交界性肿瘤(n=11)和上皮性卵巢癌(n=64),采用免疫组织化学SP法进行定性分析,然后利用RT-PCR法检测Snrvivin和MMP-9基因的表达.结果 Survivin在正常卵巢组织、卵巢良性囊肿、卵巢交界性肿瘤及卵巢癌中阳性表达率分别为20.00%、20.00%、36.67%及76.56%,MMP-9在上述各组中阳性表达率分别为25.00%、23.33%、45.45%及79.68%;与正常卵巢组织、良性上皮性卵巢囊肿比较,卵巢癌组织中Survivin和MMP-9的表达增高明显(P<0.05).Survivin、MMP-9基因的表达分别为:正常卵巢组织(0.21±0.03)、(0.23±0.03);良性卵巢囊肿(0.19±0.05)、(0.21±0.05);卵巢交界性肿瘤(0.38±0.02)、(0.44±0.02);上皮性卵巢癌(0.58±0.02)、(0.59±0.04);与正常组比较均增加,良性上皮性卵巢囊肿、卵巢癌组织中Survivin和MMP-9的表达增高明显,差异有统计学意义(P<0.05).结论 卵巢肿瘤中Survivin和MMP-9的过度表达,促进了卵巢肿瘤的形成与发展.

Abstract：

Objective To detect the expression of MMP-9 and Survivin in ovary cancer and investigate their relationship in local invasion, genesis and development of ovarian cancer. Methods The tissues samples from 64 cases of epithelial ovarian cancer,30 cases of carcinoid, 11 cases of borderline tumor and 20 cases of normal were collected, expressions of MMP-9 and Survivin were detected by immuohistochemistry SP method and RT-PCR. Results The expression positive rates of Survivin were 20.00 %, 20.00 %, 36.67 % and 76.56 %, and the positive rates of MMP-9 were 25.00 %, 23.33 %, 45.45 % and 79.68 % in normal ovarian tissues, carcinoid, borderline tumor and epithelial cancer of ovary, respectively. The positive rates of MMP-9 and Survivin were were higher in ovary epithelial cancer carcinoid than those in carcinoid and normal ovarian tissues(P <0.05). The mRNA of Survivin were (0.21 ±0.03), (0.19± 0.05), (0.38±0.02) and (0.58±0.02), and the mRNA of MMP-9 were (0.23±0.03), (0.21±0.05), (0.44±0.02) and (0.59±0.04) in normal ovarian tissues, carcinoid, borderline tumor and epithelial cancer of ovary, respectively.The mRNA levels of Survivin and MMP-9 were higher in carcinoid and epithelial cancer of ovary than those in normal ovarian tissues. Conclusion The over expressions of Survivin and MMP-9 are related to genesis and development of ovarian cancer.     

间皮素mRNA及蛋白在卵巢癌中的表达及分析

目的 研究间皮素(MESO)在卵巢癌中的表达及意义.方法 用逆转录聚合酶链反应(RT-PCR)技术和免疫组化方法分别检测卵巢肿瘤和正常卵巢组织中MESO mRNA及其蛋白水平.结果MESO mRNA和蛋白在上皮性卵巢癌(1.4005 ±0.4646,2.7857±2.2712)和交界性卵巢肿瘤(1.0650 ±0.3100,2.9167 ±2.391)中的表达水平高于良性卵巢肿瘤(0.6463±0.2419,1.2500 ±1.6125)和正常卵巢组织(0.6439 ±0.2729,0.9167 ±1.2401),差异有统计学意义(P＜0.05);MESOmRNA和蛋白在浆液性卵巢癌(1.5255 ±0.4151,3.3036 ±2.6141)和子宫内膜样癌(1.5250 ±0.5419,3.0000 ±2.3094)中的表达水平高于黏液样癌(1.0675±0.3149,1.0556 ±1.9242),差异有统计学意义(P＜0.05);临床Ⅲ、Ⅳ期MESO表达水平(1.5100 ±0.4142,3.6087 ±3.3959)高于Ⅰ、Ⅱ期(1.1190 ±0.4909,1.7895 ±2.6320),差异有统计学意义(P＜0.05).MESO表达水平与病理分级有关(P＜0.05),而与患者年龄和血清CA125水平无关(P＞0.05).结论 MESO mRNA及蛋白在卵巢癌和交界性肿瘤组表达增高,MESO可能参与卵巢癌的黏附转移.     

子宫内膜癌组织中抑癌基因PTEN突变分析

目的了解子宫内膜癌组织中磷酸酶基因PTEN突变情况及其与临床病理特征的关系.方法采用聚合酶链反应-单链构象多态性方法(PCR-SSCP)对70例子宫内膜癌组织进行PTEN基因9个外显子的突变检测.结果70例子宫内膜癌组织中PTEN基因突变率为38.57%(27/70),突变较多地分布在第5、7、8号外显子上;子宫内膜样癌突变率(44.8%)明显高于浆液性和粘液性腺癌(8.3%),P＜0.05,G1级、G2级、G3级的突变率分别为53.3%、45.5%、18.2%(P＜0.05),Ⅰ期、Ⅱ期、Ⅲ～Ⅳ期的突变率分别为52.4%、28.6%、14.3%(P＜0.05),肌层浸润程度越深,突变率越低(P＜0.05).结论PTEN基因突变是子宫内膜癌发生的早期事件,并与预后良好的临床病理特点相关.     

mRNA EXPRESSION OF PTEN AND VEGF GENES IN EPITHELIAL OVARIAN CANCER

VEGF gene, also known as vascular permeability factor, has been mapped to chromosome 6p21.3[11]. Biochemically, it is a heparin binding glycoprotein that has in at least four molecular isoforms, among which, VEGF165 occurs most common. VEGF can act as a specific mitogen for a variety of endothelial cells in vitro and as an angiogenic molecule in vivo [11,12]. VEGF is a potent multifunctional cytokine that exerts several potentially independent actions on the vascular endothelium, includin…     

Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary

Loss of heterozygosity (LOH) at locus 10q23.3 and mutation of the PTEN tumor suppressor gene occur frequently in both endometrial carcinoma and ovarian endometrioid carcinoma. To investigate the potential role of the PTEN gene in the carcinogenesis of ovarian endometrioid carcinoma and its related subtype, clear cell carcinoma, we examined 20 ovarian endometrioid carcinomas, 24 clear cell carcinomas, and 34 solitary endometrial cysts of the ovary for LOH at 10q23.3 and point mutations within the entire coding region of the PTEN gene. LOH was found in 8 of 19 ovarian endometrioid carcinomas (42.1%), 6 of 22 clear cell carcinomas (27.3%), and 13 of 23 solitary endometrial cysts (56.5%). In 5 endometrioid carcinomas synchronous with endometriosis, 3 cases displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 1 displayed no LOH events in either lesion. In 7 clear cell carcinomas synchronous with endometriosis, 3 displayed LOH events common to both the carcinoma and the endometriosis, 1 displayed an LOH event in only the carcinoma, and 3 displayed no LOH events in either lesion. In no cases were there LOH events in the endometriosis only. Somatic mutations in the PTEN gene were identified in 4 of 20 ovarian endometrioid carcinomas (20.0%), 2 of 24 clear cell carcinomas (8.3%), and 7 of 34 solitary endometrial cysts (20.6%). These results indicate that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma and clear cell carcinoma of the ovary.     

TMEFF1在卵巢上皮性浆液性肿瘤中的表达及其临床意义

目的:检测TMEFF1(tomoregulin-1)在卵巢上皮性浆液性肿瘤中的表达,探讨其临床意义.方法:采用免疫组化SP法检测卵巢上皮性浆液性囊腺癌、卵巢上皮性交界性肿瘤、卵巢上皮性良性肿瘤以及正常卵巢组织中TMEFF1的表达情况,分析其与卵巢上皮性浆液性囊腺癌临床病理参数及预后的关系.结果:TMEFF1以胞膜着色为主,亦有胞浆着色.TMEFF1在卵巢上皮性浆液性囊腺癌中的表达率(90.24%)明显高于卵巢上皮性交界性肿瘤(45.45%)、卵巢上皮性良性肿瘤(33.33%)及正常卵巢(26.67%) (P均<0.05).在卵巢上皮性浆液性囊腺癌中,TMEFF1表达随FIGO分期增加而逐渐增加(P<0.05),TMEFF1为影响卵巢上皮性浆液性癌预后的独立危险因素(P<0.05).结论:TMEFF1的表达与卵巢癌的发生、发展及预后相关.     

cDNA芯片在卵巢癌早诊及临床病理分期中的初步应用探讨

目的:探讨PTEN,nm23H₁,VEGF₁₆₅,Tiam1,MMP-2,Timp2,HE4和S100A4基因在卵巢癌发生和侵袭中的作用。方法:采用cDNA芯片技术分别检测20例卵巢癌和5例正常卵巢组织中上述基因cDNA表达谱差异。结果:PTEN,Timp2和nm23H₁ cDNA在卵巢癌组织中表达下调(CY-3/CY-5<0.5);Tiam1,VEGF₁₆₅,MMP-2,HE4和S100A4cDNA在卵巢癌组织中表达上调(CY-3/CY-5>2.0);且HE4基因表达上调的最为明显(CY-3/CY-5>5.0)。表达下调和表达上调的上述基因与卵巢癌临床病理分期、组织分化程度关系密切(P<0.01)。结论:上述基因与卵巢癌发生及侵袭关系密切。cDNA基因芯片技术对于探讨卵巢癌分子机制,寻找卵巢癌分子标志物具有重要意义。     

Early diagnosis of epithelial ovarian cancer with cDNA microarry

Objective:To investigate the roles of tumor suppressor genes-PTEN,nm23H1,VEGFl65,Tiaml,MMP-2,Timp2,HE4 and S100A4 in tumorigenesis and progression of epithelial ovarian cancer(EOC)and develop a novel method for the early diagnosis of EOC.Methods:We observed the different expression profiles of those genes in normal ovary(n=5)and ovarian cancer tissue(n=20)by eDNA microarray.Results:In EOC,PTEN,Timp2 and nm23H1 genes were down-regulated (CY-3/CY-5＜0.5),compared with the normal ovary,whereas Tiam1,VEGFl65,MMP-2,HE4 and S100A4 genes were up-regulated(CY-3/CY-5＞2.0).Among them,HE4 gene was remarkably elevated(CY03/CY-5＞5.0).Their expression was correlated with clinicopathological staging of EOC(P＜0.01).Conclusion:Those genes are closely linked to the pathogenesis and progression of EOC eDNA microarray is an effective technique to screen molecular biological markers and predict the metastastic potential of EOC in early diagnosis.     

PKP2在卵巢上皮性浆液性囊腺癌组织中的表达及临床意义

目的:探讨PKP2(Plakophilin 2)在卵巢上皮性浆液性囊腺癌组织中的表达及其与卵巢癌患者临床病理特征和预后的相关性.方法:用免疫组化SP法检测PKP2在卵巢上皮性浆液性囊腺癌(76例)、卵巢上皮性交界性肿瘤(23例)、卵巢上皮性良性肿瘤(15例)和正常卵巢(15例)组织中的表达,分析其与卵巢上皮性浆液性囊腺...     

Coexistence of malignant ovarian Brenner tumor and borderline mucinous cystadenoma,combined with primary uterine corpus endometrioid carcinoma: A case report and literature review

Malignant Brenner tumor (MBT) of the ovary is a rare malignant ovarian tumor, whereas uterine corpus endometrioid carcinoma (UEC) constitutes one of the most common malignant tumors of the female reproductive system. The present study reported on a case of the coexistence of ovarian MBT and borderline mucinous cystadenoma combined with primary UEC. Therefore, the present case is a synchronous primary cancer of both ovary and endometrium. Although synchronous primary cancers of the endometrium and ovary are relatively uncommon, they are not rare; however, due to the rarity of MBT, this case was considered singular. To the best of our knowledge, this was the first-ever reported case of the coexistence of an ovarian MBT and borderline mucinous cystadenoma combined with primary UEC. Based on a review of the literature associated with the present case, its clinicopathological features, immunohistochemical phenotype, differential diagnosis, molecular changes, prognosis and treatment were summarized and discussed. The aim of the present study was to improve the understanding of this rare synchronous primary cancer of the ovary and endometrium so as to avoid future misdiagnosis.     

FAP与TGF-β1在卵巢癌中的表达及临床意义

目的:探讨FAP、TGF-β1蛋白在卵巢癌发生发展中的作用、表达及相关病理机制。方法:采用免疫组化法检测正常卵巢（10例）、卵巢癌(50例)组织中FAP、TGF-β1蛋白表达。结果:卵巢癌组织中FAP、TGF-β1蛋白表达显著高于正常卵巢组织（P<0.05）;其蛋白表达与卵巢癌组织分化程度呈负相关（P<0.05）,与临床病理分期正相关（P<0.05）;卵巢癌组织中FAP、TGF-β1蛋白表达增高与卵巢癌淋巴结转移及有无腹水相关（P<0.05）;在卵巢癌组织中,FAP与TGF-β1蛋白表达呈正相关(r=0.605,P=0.000)。结论:在卵巢癌组织中,同时存在FAP和TGF-β1蛋白高表达,其高表达与卵巢癌的组织分化程度、临床病理分期和转移能力密切相关,可作为判定卵巢癌发生及侵袭能力的一项有效客观指标,因此,构成了卵巢癌发生和侵袭的分子基础,并有可能成为卵巢癌治疗的靶点。