细胞周期素E和P53蛋白在胃癌组织中表达及预后意义

目的 :研究细胞周期素E(cyclinE)和P53蛋白在胃癌组织中的表达水平及其与生物学行为和对预后的作用。方法 :应用免疫组化方法检测 1 2 8例胃癌组织中cyclinE和P53蛋白表达水平。 结果 :本组 1 2 8例中 ,cyclinE蛋白阳性 57例 ,占 44 .5 % ;P53蛋白阳性 67例 ,占 52 .3 % ,P53 +/cyclinE +者 48例 ,占 37.5 %。胃癌组织中cyclinE和P53蛋白表达水平与肿瘤大小、浸润深度、局部淋巴结转移、脉管侵犯和远处转移均相关。单因素生存分析显示 ,cyclinE阳性表达组五年生存率 (5 .3 % )显著低于cyclinE表达阴性组 (36 .6 % ,P <0 .0 0 1 ) ,P53蛋白表达阳性的病例五年生存率 (7.8% )显著低于P53表达阴性的病例 (2 2 .6 % ,P <0 .0 0 1 ) ,cyclinE和P53均阳性的病例五年生存率 (2 .3 % ) ,明显低于其他组的病例 (2 7.3 % ,P <0 .0 0 5)。COX模型多因素分析显示 ,cyclinE蛋白表达水平是独立的预后指标 ,P53蛋白表达水平不能作为独立的预后指标。结论 :CyclinE在胃癌中表达具有一定的预后意义 ,P53蛋白在胃癌中表达与肿瘤的生物学行为有关     

p27和cyclin E在胆囊癌中表达及与临床病理关系的研究

目的 :探讨p2 7蛋白及细胞周期素E(cyclinE)与胆囊癌发生和发展的关系。方法 :应用免疫组化SABC法检测 5 4例胆囊癌、4 8例胆囊腺瘤及 5 0例胆囊正常黏膜中p2 7及cyclinE表达情况 ,同时结合临床病理资料进行分析。结果 :5 4例胆囊癌中 ,8例 (15 % )p2 7高表达 ,4 4例 (81 4 8% )cyclinE表达 ;4 8例胆囊腺瘤中 ,2 9例 (6 0 % )p2 7高表达 ,2 7例 (5 6 2 5 % )cyclinE表达 ;5 0例胆囊正常黏膜中 ,35例 (70 % )p2 7高表达 ,2 6例 (5 2 % )cyclinE表达。p2 7蛋白在胆囊癌中的表达明显降低 ,三者之间差异有极显著意义 ,P <0 0 0 5。另外 ,p2 7在胆囊癌中表达与癌细胞的分化程度差异有显著意义 ,P <0 0 5 ;低分化癌p2 7表达较低 ,高分化与低分化的p2 7表达差异有显著意义 ,P <0 0 5。p2 7低表达的患者 1年生存率显著降低。cyclinE在胆囊癌中表达与癌细胞的分化程度和肿瘤的病理分期有关。p2 7和cyclinE在胆囊癌中表达存在着相反的联系。结论 :p2 7是细胞周期的负调控因子和潜在的肿瘤抑制因素。p2 7蛋白的降低和cyclinE的过表达在胆囊癌的发生中可能起着重要作用。p2 7是胆囊癌预后的一个可靠指标。     

p27和cyclin E蛋白表达与膀胱移行细胞癌生物学行为的关系

目的　探讨细胞周期蛋白p2 7和cyclinE表达与膀胱移行细胞癌生物学行为的关系。 方法　对 12 1例膀胱移行细胞癌进行组织病理学分级及分期 ,另取 10例正常膀胱组织作对照 ,采用免疫组织化学SABC法检测各例组织中 p2 7和cyclinE蛋白表达水平 ,并分析其表达与临床病理特征的关系。结果　p2 7和cyclinE蛋白阳性表达率分别为 42 .1% ( 5 1/12 1)和 3 4.7% ( 4 2 /12 1)。p2 7和cyclinE蛋白表达均与肿瘤的组织学分级显著相关 ,但与病理分期无关。p2 7蛋白与cyclinE蛋白表达呈负相关 (P<0 .0 5 )。p2 7阴性组中 ,cyclinE阳性患者 5年生存率低于cyclinE阴性者 (P <0 .0 5 ) ;p2 7阳性组中 ,cyclinE表达状况与患者 5年生存率无显著相关。结论　p2 7和cyclinE是评估膀胱移行细胞癌预后的有价值的指标     

胰腺癌p27~ (kip1)、cyclinE和增殖细胞核抗原的表达及与临床病理关系研究

 目的　探讨 p2 7kip1、cyclinE蛋白和PCNA在胰腺癌发生发展中的作用。 方法　应用免疫组化SP法 ,对 32例胰腺癌及癌旁组织中 p2 7kip1、cyclinE蛋白和PCNA表达进行检测。 结果　p2 7kip1蛋白阳性表达率在胰腺癌组织中为 5 6 .3% ,显著低于癌旁组织 (P <0 .0 5 ) ,并与癌组织分化程度及淋巴结转移相关 (P <0 .0 5 ) ;cyclinE和PCNA阳性表达率在胰腺癌组织中分别为6 8.8%和 71.9% ,均显著高于癌旁组织 (P <0 .0 5 ) ,并与癌组织分化程度和淋巴结转移均相关 (P <0 .0 5 )。结论　p2 7kip1、cyclinE和PC NA可能在胰腺癌发生发展中发挥重要作用。     

非小细胞肺癌bax蛋白的表达及意义

目的 :探讨凋亡相关基因bax在人非小细胞肺癌 (non smallcelllungcarcinoma ,NSCLC)组织中的表达情况及其与肺癌临床病理特征和预后的关系。方法 :用免疫组织化学SABC法检测 6 8例NSCLC中bax蛋白的表达水平 ,用TUNEL法检测其中的细胞凋亡情况。研究对象 :鳞癌 38例 ,腺癌 30例 ,同时检测 11例正常肺组织作为对照。结果bax蛋白在肺癌组织中的阳性表达率为 5 4 4 1% ,正常肺组织为 10 0 % ,两者差异有极显著性 (P <0 .0 1) ;在鳞癌中的阳性表达率为 39 4 7% ,小于腺癌的73 33% (P <0 0 1) ;bax的表达与T和N情况、临床分期、年龄、性别和是否吸烟无关。NSCLC组织的凋亡指数 (AI)为 1 79± 0 5 1,小于正常肺组织的 14 33± 5 6 2 (P <0 0 5 )。在NSCLC中 ,bax蛋白表达阴性者生存时间长于阳性者 (P <0 0 5 )。结论 :bax蛋白的表达与非小细胞肺癌的组织类型和预后相关 ,并通过对细胞凋亡的调控参与了肺癌的发生、发展。     

人非小细胞肺癌组织p63和p73的表达及意义

目的 :探讨p5 3家族新成员p6 3和p73在非小细胞肺癌 (NSCLC)中的表达及其临床意义。方法 :利用免疫组化S P法对 6 0例NSCLC和 7例正常肺组织检测p6 3和p73基因的蛋白表达。结果 :在NSCLC中 ,p6 3和p73蛋白表达的阳性率分别为 80 0 % (4 8/ 6 0 )、73 3% (4 4/ 6 0 ) ;与正常肺组织相比 ,p6 3和p73蛋白阳性表达的差异均有显著意义 ,P <0 0 5。p6 3蛋白表达与肺癌组织学类型 (P =0 0 0 0 3)和淋巴结转移有关 ,P =0 0 2 8;而与分化程度和临床分期无关 ,P >0 0 5。p73蛋白表达与肺癌组织学类型、淋巴结转移、分化程度和临床分期均无关 ,P >0 0 5。在肺癌中 ,p6 3蛋白和p73蛋白表达之间呈显著正相关 ,P =0 0 0 0 1。结论 :p6 3和p73高水平的表达协同促进肺癌的形成 ,p6 3是肺鳞癌恶性进展的一个标志物。     

环氧化酶-2在肺癌组织中的表达及其临床意义

目的　探讨环氧化酶 2 (COX 2 )在肺癌组织中的表达及其临床意义。方法　以 β actin基因为参照 ,采用逆转录聚合酶链反应 (RT PCR)技术 ,检测 41例肺癌组织及相应的癌旁组织、5例远离肿瘤的正常肺组织中COX 2mRNA的表达 ;同时用免疫组化S P法检测COX 2蛋白的表达。结果　COX 2mRNA在肺癌组织中的表达率 ( 63 .4% )显著增高 ;相应的癌旁组织表达率也明显增高 ,而在正常肺组织中不表达。癌组织与癌旁组织、正常肺组织的COX 2mRNA表达率相互比较 ,均有显著性差异 (P <0 .0 5 )。免疫组织化学检测显示 ,5 8.5 % ( 2 4/ 41)的肺癌组织COX 2蛋白呈阳性表达。COX 2蛋白的表达与肺癌的临床分期、淋巴结转移、肿瘤大小无关 (P >0 .0 5 )。结论　肺癌组织COX 2mRNA和COX 2蛋白表达率在大多数肺癌组织中明显增高 ,在癌旁病变中也相应增高 ,COX 2的激活发生在肺癌形成的较早时期 ,在肺癌发生发展中具有重要作用     

Survivin、P21WAF1/CIP1及Cyclin D1蛋白表达及与早期宫颈癌复发的关系

目的 :探讨凋亡抑制蛋白Survivin、细胞周期蛋白CyclinD1及细胞周期蛋白依赖性激酶抑制蛋白P2 1WAF1/CIP1在宫颈癌中的表达及与早期宫颈癌复发的关系。方法 :应用免疫组化S P法 ,检测Survivin、CyclinD1及P2 1WAF1/CIP1蛋白在 5 5例宫颈癌 (鳞癌 4 5例 ,腺癌 10例 )及 10例正常宫颈组织中的表达。结果 :①Survivin、CyclinD1及P2 1WAF1/CIP1蛋白在正常宫颈组织的阳性表达率分别为 0、10 0 %、2 0 0 % ;在宫颈鳞癌中阳性表达率分别为 6 8 9%、5 1 1%、5 7 8% ;在宫颈腺癌中阳性表达率分别为 6 0 0 %、90 0 %、80 0 % ;与正常宫颈组织比较 ,三者在宫颈癌中的阳性表达率明显增高 (P <0 0 5 )。②Survivin或CyclinD1蛋白的表达与鳞癌临床分期及病理分级成正相关 (P <0 0 5 ) ,而P2 1WAF1/CIP1蛋白的表达与其无关 (P >0 0 5 )。③P2 1WAF1/CIP1与Survivin或CyclinD1的共表达仅与病理分级有关 (P <0 0 5 )。而三种蛋白的共表达时与临床分期及病理分级均有关 (P <0 0 5 )。④Survivin、cyclinD1蛋白单独表达与早期宫颈癌的复发有关 (P <0 0 5 ) ,二者的共表达与早期宫颈癌的盆腔淋巴结转移有关(P <0 0 5 )。结论 :Survivin及cyclinD1蛋白在宫颈癌中的表达与临床晚期、分化不良及复     

P27kip1和cyclinE在子宫内膜癌中的表达及其意义

 目的　探讨P2 7kip1、cyclinE的表达与子宫内膜癌发生发展的关系。 方法　用免疫组化方法检测P2 7kip1和cyclinE在 4 0例子宫内膜癌、10例子宫内膜不典型增生、2 0例正常子宫内膜组织中的表达。结果　P2 7kip1在正常子宫内膜、内膜不典型增生、子宫内膜癌中的表达率分别为 90 %、70 %、6 2 .5 % ,其中子宫内膜癌与正常子宫内膜差异有显著性 (P <0 .0 5 )。cyclinE表达阳性率子宫内膜癌组显著高于内膜不典型增生组和正常子宫内膜组 (P <0 .0 5 )。P2 7kip1表达与子宫内膜癌的组织学分级、手术分期有关 (P <0 .0 5 )。P2 7kip1与cyclinE表达呈负相关。 结论　P2 7kip1、cyclinE在子宫内膜癌发生中可能起一定作用 ,P2 7kip1还与子宫内膜癌的进展有关 ,并可能成为判断预后的有用指标。     

颌骨软骨肉瘤cyclin D1和cdk4的表达及意义

 目的　分析细胞周期素D1(cyclinD1)和细胞周期素依赖激酶 (cdk4 )在颌骨软骨肉瘤的表达及意义。方法　免疫组化ABC法检测cyclinD1和cdk4在 2 0例颌骨软骨肉瘤、8例骨软骨瘤和 4例软骨瘤的表达。结果　软骨肉瘤cyclinD1和cdk4阳性表达率分别为 70 % (14 /2 0 )和 6 5 % (13/2 0 ) ,二者的阳性表达存在正相关 (rs=0 .5 2 6 ,P <0 .0 5 ) ;而它们在骨软骨瘤的阳性表达率均为 12 .5 % (1/8) ,在软骨瘤无表达 ,与软骨肉瘤相比有显著性差异 (P <0 .0 5 )。结论　CyclinD1和cdk4在颌骨软骨肉瘤过表达且与其发生和发展有关。     

cdk2 和cyclin E 在肾细胞癌中表达的意义

 目的 探讨细胞周期蛋白依赖性激酶2(cdk2)和细胞周期蛋白E(cyclin E)在肾细胞癌发病机制中的作用及其临床意义。方法 应用免疫组化方法检测cdk2、cyclin E和增殖细胞核抗原(PCNA)在48例肾细胞癌和12例正常骨组织中的表达。结果 肾细胞癌中cdk2和cyclin E表达均显著高于正常肾组织(P<0．05)。且与PCNA指数密切显著相关。但与肿瘤分级、分期、淋巴结转移及病理类型之间无显著性相关。肾细胞癌中cdk2和cyclin E共同高表达率达47．1％，且与肿瘤分级、分期和淋巴结转移之间呈正相关。结论 cdk2／cyclin E复合高表达可能在肾细胞癌发病过程中起着重要作用，联合检测两者表达水平对判断肾细胞癌生物学行为有较重要的意义。     

Analysis of cyclin E and CDK2 in ovarian cancer: Gene amplification and RNA overexpression

Cyclins and their associated kinases (cdks) play a key role in controlling the cell cycle, a process whose disregulation can potentially lead to uncontrolled cell growth and hence to cancer. We have studied the role of both cyclin E and its associated kinase cdk2 in ovarian cancer. Primary, metastatic, recurrent and benign ovarian tumors were screened for cyclin E and cdk2 gene amplification. Cyclin E was shown to be amplified in 21% and cdk2 in 6.4% of the cases analyzed. Cyclin E and cdk2 RNA expression levels were determined by semi-quantitative RT-PCR analysis in a partially overlapping series of samples and compared to the expression levels of normal ovarian surface epithelial cells. Cyclin E RNA was overexpressed in 29.5% and cdk2 in 6.5% of ovarian tumors tested. We determined that in most cases gene amplification leads to higher RNA levels for cyclin E and that the overall levels of cyclin E and cdk2 RNA were correlated. We hypothesize that cyclin E and cdk2 are, in part co-regulated and that they may concur to ovarian tumor development. Int. J. Cancer 75:34–39, 1998.© 1998 Wiley-Liss, Inc.     

Immunohistochemical study of cell cycle modulators in G1-S transition in clinical breast cancer tissue

In the present study, we investigated immunolocalization of the modulators of G(1)-S transition by using monoclonal or polyclonal antibodies for each of the modulators in 65 cases of clinical breast cancer. Two prominent cyclin dependent kinase(cdk)-cyclin complexes, cdk4-cyclin D and cdk2-cyclin E, were proved to have different modes of mutual expression. cdk4-positive lesions were found to equal cyclin D-expressing lesions in 55 cases, while the former were more extensive than the latter in 9 cases. On the other hand, cyclin E expression was detected in all the cases examined and was more dominant than that of cdk2/cdc2 in as many as 40 cases whereas the reverse was seen in only 1 case. Interestingly, cdk4(P<0.01)and cyclin E(P<0.05)expressions showed an inverse relationship with the tumor size and the cancer stage. A similar tendency was also detected for two other positive modulators of G(1)-S transition, indicating that cell cycle progression must be regulated by the cancer itself once it has grown to a certain extent. p21, which has been regarded as a universal inhibitor of the cell cycle, was expressed in 43.1% of the cases examined and its immunoreactivity showed an inverse relationship with lymph node metastasis(P<0.05). It also tended to be absent more frequently in T3 or larger cancers and stage III cases. Moreover, two patients who died as a result of cancer and three patients with recurrence were all p21 negative, suggesting that p21 is prognosticably the most significant of all these modulators.     

TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor

The present study aims to investigate expression pattern and biological roles of TRIM31 in human non-small cell lung cancer (NSCLC). We examined TRIM31 expression in 116 NSCLC tissues and 20 corresponding normal lung tissues by immumohistochemistry. We found TRIM31 downregulation in 47 out of 116 (40.5 %) cancer samples, which correlated with tumor status (p?=?0.0132), advanced p-TNM stage (p?=?0.001), and nodal metastasis (p?=?0.0382). TRIM31 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TRIM31 plasmid was performed in H157 and H1299 cells. TRIM31 overexpression inhibited cell growth rate and colony formation ability in both cell lines. In addition, expression of cell cycle regulator cyclin D1 and cyclin E were decreased after TRIM31 transfection. In conclusion, TRIM31 might serve as a tumor suppressor in non-small cell lung cancer.     

HPV16/18在膀胱癌中表达及其与bFGF、cyclinD1和cyclinE的相关关系

目的探讨人乳头瘤病毒(HPV)16/18与膀胱癌发病之间关系及其作用机制.方法应用免疫组化方法检测78例膀胱癌标本和11例正常膀胱组织中HPV16/18、碱性成纤维细胞生长因子(bFGF)、细胞周期蛋白(cyclin)D1和cyclinE的表达及相关关系.结果膀胱癌中HPV16/18阳性率为65.4%,显著高于正常的27.3%;而且与肿瘤病理分级、分期相关,但与肿瘤复发无相关.膀胱癌中HPV16/18与bFGF及cyclinD1表达之间有显著相关性,但与cyclinE表达之间无显著相关性.结论HPV16/18感染参与膀胱癌发病过程,而且通过多途径发挥作用.     

Cell cyclins and cyclin-dependent kinase activities in mouse mammary tumor development

Breast cancer in humans, as in mice and rats, is thought tobe the result of sequential changes in the epithelial cellsof the mammalian glands. This study examines the altered expressionor activation of cell cycle related proteins in an in situ systemcomposed of hyperplasia, preneoplasia and neoplasia of mousemammary glands. The results showed a high level of cdc2/cdk2kinase activities in tumors compared to hyperplasias which wasindependent of cdc2/ cdk2 protein levels. Some of the cdk-associatedproteins which are thought to regulate cdk kinase activity wereexamined in these tissues. Cyclin A was overexpressed in allhyperplasias irrespective of their tumorigenic potentials. However,a number of alterations in cyclin E protein were associatedwith cdk2 and its associated kinase activity during mammarytumorigenesis. First, the level of normal cyclin E (p50) expressionwas positively correlated with the tumorigenic potentials ofdifferent hyperplasia lines. Second, several cyclin E isoforms(p48, p43, p35, p34, p32) were detected only in tumor tissues.Third, a 2.3- and 8.3-fold increase in cyclin E-associated cdk2kinase activity was present in highly tumorigenic hyperplasiasand neoplasias respectively compared to the low tumorigenichyperplasias. Polymorphic cell nuclear antigen (PCNA) proteinbound to cdk2 was a better indicator for cell proliferationand cdk2 kinase activity than the PCNA labeling index. Theseresults suggest a sequential pattern of multiple derangementsin factors regulating cdk2 protein function during mammary tumorigenesis.High levels of cdk2 kinase activity are observed only in tumorsand appear to be closely related to alterations in cyclin Eprotein expression.     

Expression of the cell cycle regulator p27(Kip1) in normal squamous epithelium, cervical intraepithelial neoplasia, and invasive squamous cell carcinoma of the uterine cervix. Immunohistochemistry and functional aspects of p27(Kip1).

BACKGROUND: Abnormality of cell cycle regulators and tumor suppressors, such as cyclin dependent kinase inhibitors (cdkIs), has been reported in malignant tumors. The current study was undertaken to examine the involvement of a cdkI, p27(Kip1) (p27), in the neoplastic process of the uterine cervical epithelium. METHODS: Immunohistochemical staining of p27 was performed in samples of normal cervical tissue (30 samples), cervical intraepithelial neoplasias (CINs; 17 samples), and invasive squamous cell carcinoma (SCC; 25 samples). The results were compared with the expression levels of Ki-67, cdk2, and cyclin E. The functional aspects of the p27 protein, such as its ability to bind to cdk2 and the phosphorylation activity of p27-bound cdk2, also were evaluated with an immunoprecipitation and histone H1 kinase assay. RESULTS: In normal cervical epithelia, the expression of p27 was strong in the intermediate and superficial cells but very weak in the parabasal cells. In CIN samples, the expression of p27 was negligible. The expression of p27 in these tissues showed an inverse topologic correlation to that of Ki-67, cdk2, and cyclin E. However, it is noteworthy that the number of p27 positive cells increased in SCC samples that also showed increased expression of Ki-67, cdk2, and cyclin E. The p27 protein in SCC samples was bound to cdk2 and cyclin E. However, cdk2 that was bound to p27 still possessed histone H1 kinase activity. CONCLUSIONS: The expression of p27 may be involved in the growth regulation of the normal squamous epithelium in the uterine cervix. However, aberrant function of p27 expression may occur in invasive SCC of the cervix.     

Overexpression of cdk4/cyclin D1, a possible mediator of apoptosis and an indicator of prognosis in human primary lung carcinoma

The relation between expression of cell cycle-regulator molecules and apoptosis was examined in surgical specimens and cultured human lung carcinoma cell lines. Immunohistochemical analysis for 133 cases revealed 2 types of staining pattern. The first group consisted of 95 cases (71.4%) characterized by apoptotic cells showing intensely positive staining for cdk4 and cyclin D1 but negative for other proteins (type A). In the second group (type B), comprising 38 cases (28.6%), apoptotic cells exhibited intense positive staining for any cyclins and cdks. Most of the latter cases had lost expression of Rb protein. When tumor cells retrieved from paraffin-embedded tissue were examined by flow cytometry, higher proportions of cells expressing only cdk4 or cyclin D1 in type A cases and of cells expressing any cyclin or cdk in type B cases showed a subdiploid DNA content. In survival analysis using the LI of apoptotic cells and cyclin/cdk-positive cells, the high-apoptosis/high-cyclin D1 group showed the poorest prognosis. Furthermore, forced overexpression of only cdk4 or cyclin D1 induced apoptosis in cultured cells with normal Rb protein, whereas overexpression of any cyclin or cdk induced apoptosis in cells defective for Rb protein. In conclusion, upregulation of cdk4/cyclin D1 may be a primary and critical factor in induction of apoptosis in human lung carcinomas in vivo. Moreover, inactivation of Rb protein renders cells more prone to apoptosis by abnormal expression of any cell-cycle protein.     

Expression of Cyclin E and Its Relationship with the Prognosis of Patients with Breast Cancer

Objective： To investigate the expression of cyclin E in breast cancer tissues and its relationship with prognosis of the patients with breast cancer. Methods： The expression of cyclin E, HER-2/neu, nm23-H1 and actin was detected in 80 breast cancer tissues and 18 benign breast tumor tissues by immunohistochemical methods. The relationship between cyclin E and the remaining genes or the clinical data of the patients with breast cancer was analyzed. Results： The over expression rate of cyclin E in malignant tissues was obviously higher than that in benign tumor tissues （P〈0.01）. The over expression of cyclin E in later stage of disease was higher than that in early stage of disease （P〈0.05）. The expression of cyclin E in ER positive tissues was lower than that in ER negative tissues （P〈0.05）. The expression of cyclin E in PR positive tissues and PR negative tissues had no significant difference （P〉0.05）. The expression of cyclin E in HER-2/neu positive tissues was higher than that in HER-2/neu negative tissues （P〈0.05）. And the expression of cyclin E in ER, PR and HER-2/neu all positive tissues was much higher （P〈0.01）. There was no significant difference in the expression of cyclin E between nm23-H1 positive tissues and nm23-H1 negative tissues （P〉0.05）. The expression of cyclin E in actin positive and continuous distribution tissues was lower than that in actin negative or discontinuous distribution tissues （P〈0.05）. Conclusion： The expression of cyclin E has a strong correlation to the prognosis of the patients with breast cancer.