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1.
p^27Kip1和细胞周期蛋白D1在胃癌中的表达及其预后意义   总被引:5,自引:0,他引:5  
目的:研究p^27Kip1、细胞周期蛋白D1(cyclinD1)在胃癌组织中的表达水平以及与生物学行为的关系和对预后评价的意义。方法:以免疫组化方法检测92例胃癌组织中p^27Kip1、 cyclinD1蛋白的表达水平。结果:本组92例胃癌中,p^27Kip1蛋白阳性39例,占42.4%;cyclinD1蛋白表达阳性44例,占47.8%;胃癌组织中,p^27Kip1蛋白水平与胃壁浸润深度、TNM分期、病理组织学分级、区域淋巴结转移均相关(P<0.05);cyclinD1蛋白表达与病理组织学分级负相关(P<0.05);p^27Kipl与cyclinD1蛋白阳性表达显著相关(P<0.05);单变量生存分析结果,p^27Kip1高表达组三年、五年生存率分别为77.1%、57.8%,明显高于低表达组的33.7%、26.3%(P=0.007),多变量分析显示,p^27Kip1是一个独立的预后指标(P=0.0003)。结论:p^27Kip1可作为反映肿瘤恶性表型的指标,对胃癌预后具有一定的价值;cyclin1 D1是胃癌发生、发展过程中早期的分子事件;p^27Kip1在胃癌进展中起着比cyclin D1更重要的作用。  相似文献   

2.
Cyclin D1、p53及c-myc基因表达与胃癌生物学行为的关系   总被引:1,自引:0,他引:1  
目的 :探讨cyclinD1、p53及c myc基因表达与胃癌生物学行为的关系。方法 :采用S P免疫组织化学方法研究了c myc、p53及cyclinD1基因在 63例胃癌中的表达。结果 :63例胃癌中cyclinD1、P53及c myc蛋白染色阳性率分别为 32 .75 %、2 5 .40 %及 52 .38% ;最大径≥ 4cm胃癌cyclinD1、P53及c myc蛋白染色阳性率明显高于 <4cm的胃癌 (P <0 .0 5) ;≤ 49年龄组胃癌cyclinD1蛋白染色阳性率 (52 .94% )明显高于≥ 50岁年龄组 (2 3 91 % ) ;早期胃癌、侵及肌层胃癌及侵及浆膜层胃癌c myc蛋白染色阳性率分别为 35 .2 9%、44 .44%及 67.86 % ,浆膜层胃癌阳性率显著高于粘膜下层以内胃癌和肌层胃癌 (P <0 .0 5) ;高分化腺癌、低分化腺癌及粘液癌c myc蛋白染色阳性率分别为 74.0 7%、2 8.0 0 %及 54 .55 % ,三组间有显著性差异 (P <0 .0 5) ;cyclinD1、p53及c myc同时阳性者 8例 ,均为进展期胃癌 ,cyclinD1与P53、P53与c myc蛋白染色密切相关 ;cyclinD1、P53蛋白染色和胃癌的大体分型、分化程度和组织类型无明显关系 (P >0 .0 5)。结论 :cyclinD1、p53及c myc基因过表达 ,可能促使胃癌细胞增殖 ,使胃癌细胞具有更强的侵袭力  相似文献   

3.
目的 探讨胃癌及癌前病变中p16、CDK 4和cyclinD1蛋白的表达、相互关系及其意义。 方法 应用免疫组化SP法检测胃癌、不典型增生、慢性浅表性胃炎及正常胃组织中 p16、CDK4和cyclinD1蛋白的表达情况。 结果 胃癌中p16蛋白表达率为 5 2 .7% ,显著低于正常胃组织、慢性浅表性胃炎和不典型增生 (P <0 .0 1) ,而CDK 4和cyclinD1蛋白表达率分别为 61.8%、47.3 % ,均明显高于正常胃组织、慢性浅表性胃炎和轻度不典型增生 ,有显著性差异 (P <0 .0 1) ,但胃癌和中~重度不典型增生组织中CDK4和cyclinD1蛋白表达率之间无显著性差异 (P >0 .0 5 )。胃癌中p16与cyclinD1蛋白表达呈负相关关系 (P <0 .0 5 ) ,而CDK4与CyclinD1呈正相关关系 (p <0 .0 1)。 结论 胃癌发生机制涉及p16、CDK4和cyclinD1调节通路中多个基因的异常 ,且与胃癌Lauren分型、浸润深度、淋巴结转移有关。CDK4和cy clinD1蛋白高表达可能是胃癌发生过程中的早期分子事件。  相似文献   

4.
目的研究胃癌组织中p27Kip1和p53的表达与胃癌浸润、转移和预后的关系。方法用免疫组化(二步法)检测100例胃癌组织中的p27Kip1蛋白和p53蛋白的表达。结果100例胃癌组织中p27Kip1和p53蛋白阳性表达率分别为44%和49%。在胃癌深部浸润组、淋巴结转移组和5年内死亡组中p27Kip1呈显著低表达(P<0.05);在胃癌淋巴结转移组和5年内死亡组中p53呈显著高表达(P<0.05)。经单变量分析结果显示p27Kip1高表达组5年生存率为70.59%,显著高于低表达组54.55%,和阴性组26%;p53高表达组5年生存率为19.23%,显著低于低表达组43.75%和阴性组53.19%。多变量Cox回归模型分析显示p27Kip1、p53均是独立的预后指标,但p27Kip1表达对患者预后的相对危险度(RR=3.06)显著大于p53表达的相对危险度(RR=2.33,P<0.01)。结论p27Kip1低表达与p53高表达的癌细胞常更能浸润与转移,使患者生存率明显降低。p27Kip1和p53是胃癌预后的独立指标,其中p27Kip1表达评估胃癌预后的作用优于p53。  相似文献   

5.
目的:研究肝细胞癌(hepatocellular carcinoma, HCC)中PTEN、p27Kip1和cyclinD1蛋白的表达及相互关系,初步探讨它们在肝细胞癌的发生发展中的生物学意义。方法:应用Elivision免疫纽化方法检测53例肝细胞癌组织及癌旁肝组织中PTEN、p27Kip1和cyclinD1蛋白表达。结果: 53例肝细胞癌组织中p27Kip1和cyclinD1蛋白表达的阳性率分别为65%和53%,均高于癌旁肝组织(x2=34.11,x2=29.05,P值均为0.000),肝细胞癌组织中PTEN蛋白表达的阳性率(57%)明显低于癌旁肝组织中的阳性率(96.2%)(x2=20.94, P=0.000),PTEN和cyclinD1蛋白表达与肿瘤大小、TNM分期和是否伴肝硬化无关;与组织分化程度、有无侵袭性呈显著相关(P值分别为0.014、0.003、0.026和0.042)。p27Kip1蛋白表达与肿瘤大小和是否伴肝硬化无关,与肝细胞癌组织分化程度、TNM分期和有无侵袭性呈显著相关(P值分别为0.000、0.008和0.001)。PTEN蛋白表达与p27Kip1和cyclinD1蛋白表达无相关性。结论: PTEN、p27Kip1和cyclinD蛋白在肝细胞癌的发生发展中发挥重要作用。PTEN、p27Kip1和cyclinD蛋白的联合检测对评估肝细胞癌的恶性程度有参考价值。  相似文献   

6.
目的 探讨cyclinD1和p2 7蛋白在胆囊癌中的表达及意义。方法 采用免疫组化Elvision法检测 40例胆囊癌和 10例慢性胆囊炎标本cyclinD1和p2 7蛋白的表达。结果 cyclinD1的阳性表达率在胆囊癌组和胆囊炎组间有显著差异 (P <0 0 5 )。cyclinD1蛋白与胆囊癌的组织分化程度有统计学联系。p2 7蛋白的低表达率在胆囊癌组和胆囊炎组间有显著差异 (P <0 0 1) ,p2 7蛋白与胆囊癌的组织分化程度、淋巴结转移、脏器浸润和临床分期均有统计学联系。cyclinD1和p2 7蛋白的表达之间无统计学联系。结论 cyclinD1和p2 7蛋白与胆囊癌的发生可能都有密切联系 ,但二者是独立地起作用的。p2 7蛋白在一定程度上可判断患者预后。  相似文献   

7.
目的 探讨p2 1WAF1/CIP1蛋白在乳腺癌中表达的临床意义。方法 运用免疫组化SP法半定量检测p2 1蛋白在癌旁正常乳腺组织、乳腺癌组织中的表达。结果 p2 1蛋白表达位于细胞核 ,呈棕黄色。在 2 0例癌旁正常乳腺组织中 ,无p2 1蛋白表达。在 69例乳腺癌组织中有 3 0例p2 1蛋白阳性表达。在乳腺癌组织中 ,随组织学分级升高 ,p2 1阳性率下降 (P <0 0 5 ) ,随临床分期升高 ,p2 1阳性率下降 (P <0 0 5 )。有淋巴结转移组p2 1阳性率低于无淋巴结转移组 (P <0 0 5 )。p2 1蛋白阳性表达者术后 5年无瘤生存率高于p2 1蛋白阴性者术后 5年无瘤生存率 (P <0 0 5 )。结论 p2 1蛋白可用来评估乳腺癌细胞分化情况及转移潜能 ,可判断乳腺癌患者预后。  相似文献   

8.
目的研究p27kip1及cdk2在胃癌组织中的表达及其与胃癌生物学行为的关系.方法应用免疫组化SABC法检测63例胃癌组织中p27kip1及cdk2的表达.结果本组63例胃癌中,p27kip1蛋白阳性表达30例(47.6%).p27kip1与胃癌的浸润深度、淋巴结转移、组织学分级均呈负相关(P<0.05).cdk2蛋白阳性表达33例(50.8%),cdk2与胃癌的组织学分级呈正相关(P<0.05).结论提示p27kip1表达减少及cdk2表达增加可能促进了胃癌的发生发展.  相似文献   

9.
p53蛋白及cyclinD1蛋白在胃癌中的表达及临床意义   总被引:1,自引:0,他引:1  
目的通过联合检查p53蛋白及cyclinD1蛋白在胃癌组织及正常胃组织中的表达,探讨它们与胃癌分化程度的关系。方法应用流式细胞术(FCM)对13例正常胃组织及27例胃癌组织细胞进行p53蛋白及cyclinD1蛋白的检测。结果p53蛋白在正常组的表达均为阴性85.2%(23/27)的胃癌组织p53表达阳性,p53蛋白表达量(F1值)和p53蛋白阳性表达率与胃癌组织分化程度有明显相关性(P<0.01)。cyclinD1蛋白在正常组的表达均为阳性77.8%(21/27)的胃癌组织cyclinD1呈阳性表达,cyclinD1表达量(F1值)和cyclinD1阳性表达率与胃癌组织分化程度有明显相关性(P<0.01)。p53蛋白表达与cyclinD1蛋白表达呈正相关(r=0.678)。结论p53蛋白及cyclinD1蛋白过表达与胃癌组织的分化程度有明显相关性,联合检测p53及cyclinD1蛋白可做为判断胃癌恶性程度的有效指标。p53及cyclinD1蛋白的高表达与胃癌的发生、发展有密切关系。  相似文献   

10.
目的探讨p27Kip1蛋白在乳腺癌中的表达水平与乳腺癌生物学行为的关系和对预后的影响.方法用免疫组化法检测了132例乳腺癌和16例正常乳腺组织中p27Kipl蛋白的表达水平,对其中有完整随访资料的90例乳腺癌进行了临床病理学特征和生存时间关系的分析.结果p27Kip1蛋白在正常乳腺组织中高表达率为100%(16/16);在乳腺癌中高表达率为40.15%(53/132),低表达率为59.85%(79/132),差异有显著性(P<0.005).不同类型的乳腺癌中p27Kip1蛋白的表达水平差异无显著性(P>0.1).乳腺癌组织p27Kipl蛋白表达水平与病理组织学分级、肿瘤内坏死、核分裂数、腋淋巴结转移情况、局部复发和远处转移显著相关(P<0.005),与肿块大小、年龄、ER水平、月经状况无显著关系.生存关系分析显示p27Kip1蛋白低表达的乳腺癌患者生存率明显低于p27Kipl蛋白高表达者(P<0.001).Cox模型则显示p27Kip1蛋白是乳腺癌的一个独立的预后标志物.结论①p27Kip1蛋白的表达水平与乳腺癌的组织学类型无关;②p27Kip1蛋白是检测乳腺癌预后有价值的独立指标,有助于临床选择高危复发病例;③p27Kip 1蛋白表达水平可做为术后进一步治疗的参考指标.  相似文献   

11.
BACKGROUND AND OBJECTIVES: Altered expression of cell-cycle regulators is prevalent in clinical breast cancer. This study was performed to analyze the impact of cyclin E expression to the outcome of breast cancer together with cyclin D1 and p27Kip1. METHODS: The correlation between cyclin D1/E and p27Kip1 expression was analyzed in tissue arrays of 175 node-negative breast cancers treated by the same chemotherapy composed of fluorouracil, cyclophosphamide, and methotrexate. Data from the immunohistochemical assays of three molecules were correlated and were analyzed with clinical outcome of the patients. RESULTS: Cyclin E expression was observed in 48 (27.4%) of 175 breast carcinomas. Cyclin E expression was significantly increased in young age patients and poorly differentiate tumors. Expression of cyclin E was significantly increased in cyclin D1 expressing tumors (P = 0.034). p27Kip1 expression was preserved above the 50% level in 87 tumors (49.7%) and was inversely correlated with cyclin E expression (P = 0.042). Ki67 labeling index was significantly increased in cyclin E-expressing tumors (P = 0.033) and was inversely related with p27Kip1 expression. In multivariate survival analysis, cyclin E expression was significant for the prediction of poor survival of the patients. CONCLUSIONS: Cyclin E expression was associated with poor prognosis and intimately correlated with the expression of cyclin D1 and p27Kip1. Integration of TMA technology allowed a high-throughput analysis for correlating molecular in situ findings with clinico-pathologic information.  相似文献   

12.
To elucidate carcinogenesis in the endometrium, we investigated cyclin D1 immunoreactivities in 20 normal endometria, 20 endometrial hyperplasias and 141 endometrioid-type endometrial adenocarcinoma. We also evaluated the correlation of cyclin D1 expression with Ki-67, cyclin E, cyclin A, cdk2, p27 and p53, and clinicopathological parameters and prognosis. Cyclin D1 expression increased significantly with histological grade, and the labeling index (LI) for cyclin D1 was 121 +/- 23.4% in G1, 12.7 +/- 23.7% in G2 and 15.7 +/- 18.5% in G3. The LIs were significantly correlated with those for cyclin E, cyclin A and Ki-67, but not with the LIs of cdk2, p27 or p53. In contrast, high cyclin D1 expression was significantly correlated with low p53 expression. Cyclin D1 expression was not significantly correlated with any of the clinicopathological parameters except histological grade. Cyclin D1 expression was significantly correlated with histological grade and proliferative activity, but not clinicopathological parameters and prognosis in endometrial adenocarcinoma.  相似文献   

13.
The protein p27Kip1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas (P<0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.  相似文献   

14.
The protein p27Kp1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas ( P <0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.  相似文献   

15.
Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.  相似文献   

16.
BACKGROUND AND OBJECTIVES: p27Kip1 is an inhibitor of cyclin-dependent kinases and is speculated to be a potential prognostic indicator in numerous human cancers. We investigated expression of p27Kip1 along with cyclin D1 in gastric cancer to estimate the clinical utility of p27Kip1. METHODS: Immunohistochemical assay for p27Kip1 and cyclin D1 proteins was performed in 64 patients with primary gastric cancer. Correlation between p27Kip1 expression and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients and cyclin D1 was overexpressed in 22 (34.4%) out of 64. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P = 0.015) and was also reduced in the tumors with high S-phase fraction (86.7%, 26/30) compared with tumors showing low S-phase fraction (41.2%, 14/34; P = 0.0002). Expression of p27Kip1 and cyclin D1 was inversely correlated (P = 0.021). In univariate analysis, extent of the disease (P < 0.001), expression of cyclin D1 (P = 0.0001), and reduced expression of p27Kip1 (P = 0. 0006), were statistically significant to predict patient's outcome, but depth of invasion (P = 0.008) and pathologic stage (P = 0.009) emerged as significant prognostic indicators in multivariate analysis. CONCLUSION: Expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 seems to have potential as a prognostic marker in the management of gastric cancer patients.  相似文献   

17.
细胞周期调控因子与下咽癌生物学行为相关性初步研究   总被引:1,自引:0,他引:1  
目的:探讨细胞周期调控因子与下咽癌临床生物学行为之间的关系。方法:取下咽鳞状细胞癌手术标本53例,癌旁正常粘膜标本11例,应用免疫组化SP法检测P27^Kipl、Cyelin D1、CDK4在下咽癌组织及正常粘膜中的表达。结果:P27^Kipl、CyclinD1、CDK4均为弥漫性细胞核表达。P27^Kipl。在下咽癌中的表达低于正常粘膜.且表达与N分级明显相关(P〈0.05);CyclinD1在下咽癌中的表达高于正常粘膜,且表达与T分级明显正相关(P〈0.05):CDK4在下咽癌中的表达高于正常粘膜,且表达与T分级、N分级明显正相关(P〈0.01、P〈0.05)P27^Kipl与CyclinD1.P27^Kipl与CDK4在下咽癌组织中多呈反向表达,CyclinD1与CDK4多呈同向表达。结论:CyclinD1、CDK4与P27^Kipl在下咽癌发病机制中共同作用.对预后有一定的参考价值。  相似文献   

18.
Migita T  Oda Y  Naito S  Tsuneyoshi M 《Cancer》2002,94(4):973-979
BACKGROUND: Proliferative activity in tumors depends on regulation of the cell cycle. p27(Kip1) (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS: Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS: In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS: The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma.  相似文献   

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