细胞周期素D1与p53蛋白在卵巢上皮性肿瘤的表达及意义

目的　探讨细胞周期素D1(CyclinD1)与 p5 3蛋白在卵巢上皮性肿瘤的表达及意义。 方法　 1990～1995年应用免疫组化法对 4 0例恶性卵巢上皮性肿瘤及 2 0例良性卵巢上皮性肿瘤组织进行CyclinD1与 p5 3蛋白检测。结果　良性卵巢上皮性肿瘤CyclinD1阳性表达为 10 0 % ,而恶性卵巢上皮性肿瘤CyclinD1阳性表达为37 5 %。良性卵巢上皮性肿瘤p5 3阳性表达为 15 0 % ,恶性卵巢上皮肿瘤 p5 3阳性表达为 4 7 5 %。CyclinD1在卵巢上皮癌G1与G2 、G3 中的阳性表达统计学差异有显著性 (P <0 0 5 ) ,p5 3蛋白在早期卵巢上皮癌与晚期卵巢上皮癌组织中的阳性表达 ,统计学差异有显著性 (P <0 0 5 ) ,p5 3蛋白的阳性表达在卵巢癌G1与G2 、G3 比较差异有显著性 (P <0 0 5 )。CyclinD1过表达的细胞同时也有 p5 3的过表达。 结论　CyclinD1与 p5 3蛋白在卵巢上皮性肿瘤的共同表达可能是促进卵巢上皮性肿瘤发展的因素。     

细胞周期素D1与p53蛋白在卵巢上皮性肿瘤的表达及意义

目的探讨细胞周期素D1(CyclinD1)与p53蛋白在卵巢上皮性肿瘤的表达及意义.方法 1990～1995年应用免疫组化法对40例恶性卵巢上皮性肿瘤及20例良性卵巢上皮性肿瘤组织进行CyclinD1与p53蛋白检测.结果良性卵巢上皮性肿瘤CyclinD1阳性表达为10.0%,而恶性卵巢上皮性肿瘤CyclinD1阳性表达为37.5%.良性卵巢上皮性肿瘤p53阳性表达为15.0%,恶性卵巢上皮肿瘤p53阳性表达为47.5%.CyclinD1在卵巢上皮癌G1与G2、G3中的阳性表达统计学差异有显著性(P<0.05),p53蛋白在早期卵巢上皮癌与晚期卵巢上皮癌组织中的阳性表达,统计学差异有显著性(P<0.05),p53蛋白的阳性表达在卵巢癌G1与G2、G3比较差异有显著性(P<0.05).CyclinD1过表达的细胞同时也有p53的过表达.结论 CyclinD1与p53蛋白在卵巢上皮性肿瘤的共同表达可能是促进卵巢上皮性肿瘤发展的因素.     

细胞周期素Dl与p53蛋白在卵巢上皮性肿瘤的表达及意义

目的：探讨细胞周期素D1(CyclinD1)与p53蛋白在卵巢上皮性肿瘤的表达及意义。方法：1990--1995年应用免疫组化法对40例恶性卵巢上皮性肿瘤及20例良性卵巢上皮性肿瘤组织进行CyclinD1与p53蛋白检测。结果：良性卵巢上皮性肿瘤CyclinD1阳性表达为10．0％，而恶性卵巢上皮性肿瘤CyclinD1阳性表达为37．5％。良性卵巢上皮性肿瘤p53阳性表达为15．0％，恶性卵巢上皮肿瘤p53阳性表达为47．5％。CyclinD1在卵巢上皮癌Gl与G2、G3中的阳性表达统计学差异有显著性(P＜0．05)，p53蛋白在早期卵巢上皮癌与晚期卵巢上皮癌组织中的阳性表达，统计学差异有显著性(P＜0．05)，p53蛋白的阳性表达在卵巢癌G1与G2、G3比较差异有显著性(P＜0．05)。CyclinD1过表达的细胞同时也有p53的过表达。结论：CyclinD1与p53蛋白在卵巢上皮性肿瘤的共同表达可能是促进卵巢上皮性肿瘤发展的因素。     

p27kip1蛋白在卵巢上皮癌中的表达及其临床意义

目的 :研究p2 7kip1在卵巢上皮癌中的表达及其临床意义。方法 :采用免疫组化SP法检测 2 0例卵巢良性、5 8例卵巢恶性上皮性肿瘤中p2 7kip1蛋白的表达。应用Kaplan Meier法及Cox比例风险回归模型 ,分析p2 7kip1蛋白表达与卵巢上皮癌患者预后的关系。结果 :(1)卵巢良性和恶性上皮性肿瘤中p2 7kip1蛋白表达阳性率分别为75 .0 % ,4 6 .6 % ,恶性肿瘤中p2 7kip1蛋白表达阳性率明显低于良性肿瘤 ,恶性肿瘤染色阳性部位以胞浆为主 ;(2 )p2 7kip1蛋白的表达与病理学分级有关 ,与年龄、临床分期、淋巴结转移、组织学亚型无关 ;(3)卵巢上皮癌中 ,p2 7kip1蛋白的表达与bax蛋白的表达呈正相关 ,与bcl 2蛋白的表达呈负相关 ,与ki6 7蛋白无明显相关性 ;(4)p2 7kip1蛋白表达是影响卵巢上皮癌患者预后的独立因素 ,阳性者预后较好。结论 :p2 7kip1蛋白可能与卵巢上皮癌的发生有关。p2 7kip1蛋白可作为判断患者预后的指标。     

p27kip1及p53基因蛋白与恶性卵巢上皮性肿瘤预后的关系

目的　探讨 p2 7kip1和 p5 3基因蛋白在恶性卵巢上皮性肿瘤中的表达及其与预后的关系。 方法　1992年 11月至 1999年 12月应用免疫组化检测 5 6例恶性卵巢上皮性肿瘤石蜡切片中 p2 7kip1和p5 3基因蛋白表达情况 ,并应用Kaplan -Mier法及多变量Cox比例风险回归模型分析患者预后。 结果　 5 6例恶性卵巢上皮性肿瘤患者的 p2 7kip1基因蛋白表达率为 4 1 1% ;p5 3基因蛋白表达率为 4 8 2 % ,两种基因蛋白表达比较 ,差异无显著性 (P >0 0 5 )。p2 7kip1及 p5 3基因蛋白表达与肿瘤的病理分级有关 ( P <0 0 5 ) ,与其他临床病理特征无关。单因素分析 :p2 7kip1及 p5 3基因蛋白表达与患者的中位生存时间、生存曲线各时点生存率密切相关。 结论　p2 7kip1基因蛋白表达对恶性卵巢上皮性肿瘤的预后有显著影响 ,而 p5 3基因蛋白表达与预后关系不显著     

卵巢上皮性肿瘤中细胞周期素D1蛋白与p16蛋白的表达及其临床意义

目的　探讨细胞周期素D1蛋白 (cyclinD1)与 p16蛋白在卵巢上皮性肿瘤中的表达及临床意义。 方法　 1998年 1月至 2 0 0 0年 1月采用免疫组化SP法 ,检测恶性、交界性、良性卵巢上皮性肿瘤、正常卵巢组织中的cyclinD1蛋白和p16蛋白的表达。结果　cyclinD1蛋白、p16蛋白表达的阳性率分别为恶性 5 0 %和 4 0 %、交界性30 %和 5 0 %、良性卵巢上皮性肿瘤 0和 80 %、正常卵巢组织中 0和 90 %。恶性卵巢上皮性肿瘤与良性卵巢上皮性肿瘤及正常卵巢组织之间比较 ,cyclinD1蛋白的表达差异有显著性意义 (P <0 0 1) ,p16蛋白的表达差异有显著性意义 (P <0 0 5 )。在恶性程度较高 ,组织分化差 ,晚期的恶性卵巢上皮性肿瘤中cyclinD1蛋白表达率高 ,p16蛋白的表达率低。相关性分析显示 ,cyclinD1蛋白与 p16蛋白的表达呈负相关。 结论　cyclinD1蛋白的过度表达与 p16蛋白表达的缺失在恶性卵巢上皮性肿瘤的发生、发展中起一定作用 ,二者可能存在相互抑制机制。     

细胞周期素D1蛋白在卵巢上皮性肿瘤中的表达及其意义

目的　研究细胞周期素D1(cyclinD1)在卵巢上皮性肿瘤中的表达及意义。方法　 1997～ 2 0 0 0年采用免疫组织化学SP法 ,检测恶性卵巢上皮性肿瘤、交界性肿瘤、良性肿瘤、正常卵巢组织cyclinD1的表达。结果　在恶性卵巢上皮性肿瘤 ,良性肿瘤 ,正常卵巢组织之间cyclinD1的表达差异有显著性 (P <0 0 1)。cyclinD1的表达率与组织分化程度和临床分期有显著相关性 (P <0 0 5 ) ,cyclinD1的过度表达见于组织分化差 ,肿瘤发病的晚期。结论　cyclinD1在卵巢癌组织中广泛存在 ,并与组织分化 ,临床分期有一定相关性 ,提示该基因在卵巢癌的发生、发展中起一定作用     

卵巢上皮性肿瘤中黏蛋白MUC2和MUC5AC的表达及意义

目的 研究卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达，探讨它们在卵巢上皮性肿瘤恶性进展中的作用及其临床意义。方法 采用免疫组化方法SP法检测20例良性、23例交界性和37例恶性卵巢上皮性肿瘤中黏蛋白MUC2和MUCSAC的表达。结果 黏蛋白MUC2和MUCSAC表达水平随卵巢黏液性肿瘤恶性程度的增加而表达增高。黏蛋白MUC2的表达与肿瘤的病理分级和临床分期密切相关，而黏蛋白MUCSAC与病理分级和临床分期无关。结论 卵巢黏液性肿瘤发生早期肿瘤细胞即有胃型和肠型的分化，并且随着肿瘤的恶性进展持续存在。检测黏蛋白MUC2的表达可作为预测卵巢癌预后的有价值的指标。。     

PED/PEA-15及其磷酸化状态在卵巢上皮肿瘤中的表达及意义

目的:探讨PED/PEA-15(phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes)蛋白及其磷酸化状态在卵巢上皮性肿瘤中的表达及临床意义。方法:免疫组化法检测40例卵巢上皮良性肿瘤(良性组)、40例卵巢交界性肿瘤(交界性组)、50例卵巢上皮癌(恶性组)中PED/PEA-15及其磷酸化状态的阳性表达水平。结果:PEA-15蛋白在良性组中表达高于交界性组及恶性组(P0.05),且在卵巢癌组中随着卵巢癌恶性程度的增高及临床分期的发展而降低(P0.05),但与患者年龄无明显相关性(P0.05)。卵巢癌中PEA-15磷酸化状态p PEA-15-Ser104蛋白表达高于交界性及良性上皮肿瘤(P0.05)。卵巢癌组织中p PEA-15-Ser104蛋白表达与组织学分级和临床分期有关(P0.05),但与有无淋巴结转移及年龄无明显相关性(P0.05);另一位点磷酸化状态p PEA-15-Ser116在不同性质卵巢组织、不同年龄、组织学分级、临床分期、淋巴结转移分组中表达无差异(P0.05)。结论:PEA-15及其磷酸化状态在卵巢癌的发生发展中发挥重要作用,可否通过调控PED/PEA-15的磷酸化状态从而使之成为卵巢癌治疗的重要靶点仍需进一步研究。     

CyclinD1、C-erbB2及bcl-2基因在卵巢上皮性肿瘤中的表达及其临床意义

目的 :检测癌基因CyclinD1、C erbB2及bcl 2在卵巢上皮肿瘤中的表达 ,探讨它们在卵巢肿瘤发生、发展中的作用及临床、病理意义。方法 :应用免疫组化SP法检测72例恶性卵巢肿瘤、12例交界性卵巢肿瘤、2 1例良性肿瘤及 10例正常卵巢组织中Cy clinD1、C erbB2及bcl 2基因的表达情况。结果 :1.卵巢恶性、交界性及良性肿瘤中Cy clinD1阳性率依次为 2 7.78%、33.3%、9.5 2 %。恶性及交界性肿瘤阳性率明显高于良性肿瘤 ,其阳性率与组织学分级呈负相关 ,而与患者年龄、临床分期、组织学类型无关 ;2 .卵巢恶性、交界性及良性肿瘤中C erbB2的阳性率依次为 5 6 .9%、4 1.6 7%、14.2 8%。恶性及交界性肿瘤阳性率明显高于良性肿瘤 ,差异有显著性。C erbB2阳性表达在组织分化差及期别晚的肿瘤中较分化好、期别早者高 ;3.卵巢恶性、交界性、良性肿瘤中bcl 2的阳性表达率依次为 6 3.89%、5 0 %、2 8.5 %。恶性及交界性肿瘤与良性肿瘤之间的表达差异有显著性。组织分化差、期别早的肿瘤中bcl 2的阳性率较分化好、期别晚者高 ;4 .两种及两种以上基因同时表达率 (5 1.4 % )显著高于单基因表达 (2 7.79% )。CyclinD1与C erbB2基因表达呈负相关。结论 :CyclinD1、C erbB2及bcl 2基因在卵巢癌发生、发展中起重要作用 ,表明细胞?     

上皮性卵巢肿瘤cyclin B1和p27的表达及其意义

目的:探讨cyclin B1和p27在上皮性卵巢肿瘤发生、发展及预后中的作用。方法:应用免疫组化S-P法检测正常卵巢(20例)、良性上皮性卵巢肿瘤(20)及恶性上皮性卵巢肿瘤(20例)中cyclin B1和p27的表达,分析其表达水平与肿瘤恶性程度、临床分期及淋巴转移间的关系。结果:cyclin B1在恶性上皮性卵巢肿瘤中的表达水平高于正常卵巢和良性肿瘤,差异有显著性(P<0.05);p27在正常卵巢、良性肿瘤和恶性肿瘤中的阳性表达呈显著性递减趋势(P<0.05);cyclin B1表达与肿瘤的临床分期及淋巴转移显著相关(P<0.05)。结论:cyclin B1高表达和p27低表达,可能与卵巢肿瘤的发生、发展密切相关。     

Implication of malignancy and prognosis of p27(kip1), Cyclin E, and Cdk2 expression in epithelial ovarian tumors

OBJECTIVE: The aim of this study was to further evaluate whether the expression of p27(kip1), cyclin E, and cdk2 is related to the malignancy of ovarian tumors and whether their expressions, alone or in combination, are associated with prognosis in epithelial ovarian carcinoma. METHODS: Immunohistochemical analysis using anti-p27(kip1), anti-cyclinE, and anti-cdk2 antibodies was carried out for 103 cases consisting of benign, borderline, and malignant ovarian tumors, and Western blot analysis and cdk2 activity assay were performed in 26 fresh ovarian tumor samples. RESULTS: p27(kip1) expression was reduced in ovarian carcinomas in contrast to benign and borderline tumors. The expression of cyclin E and cdk2 gradually increased from benign to borderline to malignant tumors. Kaplan-Meier survival analysis showed that patients with p27(kip1) expression had a high overall survival rate. Patients with cyclin E overexpression had a low overall survival rate. When the combination of these proteins was analyzed, patients with the p27(kip1) (-)/cyclin E (++)/cdk2 (++) phenotype were significantly associated with the poorest overall survival. In multivariate Cox regression analysis, the combined phenotype of p27(kip1) (-)/cyclin E (++)/cdk2 (++) was independently related to poor prognosis. CONCLUSIONS: Our results suggest that loss of p27(kip1) expression and overexpression of cyclin E or cdk2 were significantly associated with malignancy in ovarian tumors. p27(kip1) and cyclin E proteins may be valuable prognostic factors for epithelial ovarian carcinoma patients. Furthermore, the combined evaluation of p27(kip1)/cyclin E/cdk2 may provide the most important prognostic implication.     

The concurrent expression of p27(kip1) and cyclin D1 in epithelial ovarian tumors.

Mammalian cell-cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (cdks) and cdk inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address alterations and roles of these cell-cycle proteins in the development of epithelial ovarian carcinomas, we analyzed the expression of the p27(kip1), cyclin D1, cyclin E, and cdk2. A panel of 79 epithelial ovarian tumors was selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to p27(kip1), cyclin D1, cyclin E, and cdk2. The results showed that p27(kip1) and cyclin D1 were concurrently expressed in epithelial ovarian tumors, and the expression was down-regulated in ovarian carcinomas. There was an inverse relationship between the expression level of p27(kip1) and cyclin D1 and the histological tumor grades. On the other hand, the expression of cyclin E and cdk2 was enhanced in ovarian carcinomas. The results suggest that low expression of p27(kip1) and cyclin D1 as well as high expression of cyclin E and cdk2 promotes the development of ovarian tumors. p27(kip1) and cyclin D1 expression are negatively correlated with the malignant degree of epithelial ovarian tumors. Thus, the ovarian tumors with high p27(kip1) and cyclin D1 expression may generally have a somewhat better prognosis, while those with low p27(kip1) and cyclin D1 expression may have a worse prognosis.     

Cyclin D1 overexpression and p53 mutation status in epithelial ovarian cancer

OBJECTIVE: To examine the cyclin D1 mRNA expression level in ovarian tumor samples as compared with normal ovaries and to determine the relationship between cyclin D1 overexpression and p53 mutation status in ovarian tumors. METHODS: mRNA was isolated and cDNA was prepared from 27 epithelial ovarian tumors (3 tumors of low malignant potential (LMP) and 24 cancers) and 6 normal ovaries. The cyclin D1 sequences were amplified by using a thermal cycler in parallel with the beta-tubulin gene as an internal control. The cyclin D1 mRNA expression level relative to beta-tubulin was determined by 32P phosphoimager analysis. To confirm the overexpression of the cyclin D1 protein in ovarian tumor cells, immunostaining was performed. The p53 gene mutation status was examined by direct cDNA sequencing. RESULTS: mRNA levels of cyclin D1 were significantly higher in 21 (78%) of the 27 ovarian tumors than in normal ovaries. Cyclin D1 overexpression was detected in ovarian LMP tumors as well as in ovarian cancer cases. Positive immunostaining of cyclin D1 protein was observed in 10 of 18 (56%) ovarian tumors examined. p53 mutations were found in 11 (61%) of 18 ovarian tumors. Of 11 ovarian tumor cases with p53 mutations, 5 showed overexpression of cyclin D1. All 7 ovarian tumor cases without p53 mutations showed significant cyclin D1 mRNA overexpression. CONCLUSION: Cyclin D1 overexpression seems to be an early genetic event in ovarian tumor development. Although p53 may be one of the proteins whose function regulates the expression of G1 cyclins, ovarian tumors with no p53 mutation consistently showed cyclin D1 overexpression. Cyclin D1 overexpression may play an important role in the tumorigenesis of epithelial ovarian tumors.     

卵巢上皮癌组织中MT1-MMP的表达及意义

目的　探讨膜型基质金属蛋白酶 - 1(membranetype - 1matrixmetalloproteinase,MT1-MMP)在卵巢上皮癌组织中的表达及其与肿瘤生物学行为和预后的关系。方法　用免疫组化SP法检测 5 6例卵巢上皮癌组织、 15例卵巢良性肿瘤组织以及 10例正常卵巢组织中MT1-MMP蛋白的表达。结果　 6 7 9%的卵巢上皮癌组织MT1-MMP表达阳性 ,卵巢良性肿瘤组织很少表达 (4/ 15 ) ,正常卵巢组织中几乎不表达 (1/ 10 ) ,差异有显著性 (P <0 0 1)。MT1-MMP的表达水平与临床分期、组织学分级以及淋巴结转移密切相关。在单因素生存分析中 ,MT1-MMP的表达与患者预后不良有关。但是 ,在多因素分析中 ,MT1-MMP的表达并不是一个相对独立的预后因素。结论　①MT1-MMP在卵巢上皮癌中异常高表达 ;②MT1-MMP表达促进卵巢癌的侵袭和转移 ,可作为判断卵巢癌恶性表型的有用指标 ;③MT1-MMP的阳性表达与患者不良预后有关。     

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。     

Overexpression of cyclin D1 and c-Myc gene products in human primary epithelial ovarian cancer

Cyclin D1 and c-Myc are key participants in the cell-cycle pathway, in which aberrancies have been associated with malignant transformation. To date, data on the relationship of expression of these proteins and histologic subtype of epithelial ovarian cancer are still scarce and discordant. Immunohistochemical analysis was performed on 12 normal ovaries and 47 cases of serous, mucinous, endometrioid, and clear cell ovarian carcinomas. No abnormal expression of cyclin D1 or c-Myc was demonstrated in any of the 12 normal ovarian specimens. However, compared to normal ovarian tissues, overexpression of cyclin D1 and c-Myc was observed in 42.6% (20/47) and 65.9% (31/47) of tumors examined, respectively. There was no significant difference of overexpression of cyclin D1 or c-Myc gene products between these four histologic subtypes of ovarian adenocarcinomas. This study shows that cyclin D1 and c-Myc are frequently overexpressed in epithelial ovarian carcinomas, but they are not correlated with a particular histologic subtype. Although our preliminary results need to be validated in a larger number of tumors, the abnormal expression of cyclin D1 and c-Myc in epithelial ovarian cancer reaffirms the notion that they are crucial components in the pathway of tumorigenesis and deserve further study.