p21WAF1、Cyclin D1和PRb在膀胱移行细胞癌中的表达及其意义

目的 :探讨 p2 1WAF1、细胞周期蛋白 D1 (Cyclin D1 )和 PRb在膀胱移行细胞癌(BTCC)中的表达及相互关系及其意义。方法 :应用免疫组织化学 SP法检测 5 7例 BTCC患者癌组织中 p2 1WAF1、Cyclin D1 和 PRb的蛋白表达。结果 :p2 1WAF1、Cyclin D1 和 PRb的阳性表达率分别为36 .8%、49.1%和 45 .6 % ,p2 1WAF1随病理分级升高阳性率显著下降 ,Cyclin D1 和 PRb的表达与BTCC的病理分级、临床分期和有无转移均相关 ,p2 1WAF1与 PRb的表达呈负相关 ,Cyclin D1 和PRb的表达呈正相关 ,而 p2 1WAF1与 Cyclin D1 的表达无关。结论 :p2 1WAF1/ Cyclin D1 / PRb通路异常与 BTCC的发生发展密切相关 ,p2 1WAF1的改变可能为癌变的早期事件 ,联合检测 p2 1WAF1、Cyclin D1 和 PRb可较准确地评价 BTCC的生物学特性 ,估计预后 ,指导治疗     

胃癌中p21WAF1/CIP1、细胞周期素D1、p53表达的相关性

目的　探讨p2 1WAF1/CIP1、细胞周期素D1(cyclinD1)、p5 3在胃癌中表达之间的相关性。 方法　应用原位杂交技术检测p2 1WAF1/CIP1mRNA、细胞周期素D1mRNA及免疫组化技术检测p5 3蛋白在胃癌中的表达。结果　p2 1WAF1/CIP1mRNA在癌组织及癌旁正常粘膜中阳性表达率各为 93.15 % (6 8/73)及76 .71% (5 6 /73) ,二者相比具有显著差异 (P <0 .0 5 )。CyclinD1mRNA在癌组织及癌旁正常粘膜中阳性表达率各为 5 4 .79% (40 /73)及 30 .16 % (2 2 /73) ,二者具有显著差异 (P <0 .0 5 )。p5 3蛋白在胃癌中的阳性表达率为 32 .87% (2 4 /73) ,p5 3过表达者 ,其 p2 1WAF1/CIP1mRNA表达较p5 3阴性者为低 ,二者存在显著差异 (P <0 .0 5 )。p2 1WAF1/CIP1表达与细胞周期素D1表达呈负相关。结论　p2 1WAF1/CIP1、CyclinD1、p5 3的异常表达及它们之间可能存在的相互作用 ,对于胃癌的发生发展具有重要意义。     

pRb2/p130、cyclin D1和MUC1在食管鳞癌中的表达

 目的探讨pRb2/p130、cyclinD1和MUC1在食管鳞癌中的表达及意义。方法应用免疫组化法检测了pRb2/p130、cyclinD1和MUC1在16例正常食管粘膜上皮及60例食管鳞癌中的表达水平,分析它们与临床病理指标及其三者之间相关关系。结果食管鳞癌中pRb2/p130的低表达与癌组织分化程度、TNM分期、淋巴结转移、浸润深度有关;cyclinD1的高表达与癌组织的分化程度、淋巴结转移相关;MUC1的高表达与淋巴结转移相关;Kaplan-Meier生存分析表明pRb2/p130高表达组生存率高于低表达组(P=0.0032,LogRank检验);Cox比例风险模型分析显示pRb2/p130、淋巴结转移、癌组织的分化程度是食管鳞癌的独立预后指标。结论食管鳞状细胞癌中存在pRb2/p130的低表达以及cyclinD1和MUC1的高表达,促进了细胞的生长和肿瘤的发展,是食管癌发生发展中的重要事件。     

胃癌及癌前病变中p16、p21~(WAF1)、CDK4、cyclinD1蛋白的表达及其意义

目的:探讨胃癌及癌前病变中p16、p21WAF1、CDK4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、p21WAF1、CDK4和cyclinD1蛋白的表达情况。结果:胃癌中p16和p21WAF1蛋白表达率分别为:52.7%、30.9%,显著低于慢性浅表性胃炎和不典型增生(P<0.01),而CDK4和cyclinD1蛋白表达率分别为:61.8%、47.3%,均明显高于正常胃组织和慢性浅表性胃炎,差异有显著性(P<0.01),但胃癌和不典型增生组织中CDK4和cyclinD1蛋白表达率之间差异无显著性(P>0.05)。胃癌中p16与cyclinD1蛋白表达呈负相关关系(P<0.05),而CDK4与cyclinD1呈正相关关系(P<0.01)。结论:胃癌发生机制涉及p16、p21WAF1、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cyclinD1蛋白高表达可能是胃癌发生过程中的早期分子事件。     

p16、p21^WAF1／CIP1、CyclinD1表达与乳腺癌病理特征

目的　探讨乳腺癌组织分型、分级等临床病理特征和ER、PR与p16、p2 1WAF1/CIP1和CyclinD1蛋白表达的关系。方法　进行免疫组化染色法检测 5 0例术前均未作放化疗的乳腺癌组织中p16、p2 1WAF/CIP1和CyclinD1蛋白的表达。结果　p16蛋白表达阳性率为 5 8 0 % (2 9/ 5 0 ) ,在浸润性导管癌Ⅱ级与Ⅲ级之间p16蛋白表达有显著性差异 (P <0 0 5 ) ,阳性率分别为 75 0 %、41 7%。p16、p2 1CyclinD1蛋白表达 ,p2 1蛋白表达阳性率为 30 0 % (15 / 5 0 ) ,p2 1表达阳性者与阴性者相比 ,淋巴结转移率有显著性差异 (P <0 0 5 )。CyclinD1蛋白表达阳性率为 32 0 % (16 / 5 0 )。与临床病理特征、ER和PR未见相关 (P >0 0 5 )。结论　p16和p2 1蛋白可作为判断肿瘤生物学行为的参数。     

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     

原发性肝细胞癌组织中p53和p21WAF/CIP1及MDM2蛋白的表达及其临床意义

目的探讨p53、p21WAF/CIP1及MDM2蛋白在原发性肝细胞癌(hepatocellular carcinoma, HCC)组织中的表达及其临床病理意义.方法选取115例HCC及其相应的癌旁肝组织构建组织芯片,应用免疫组织化学方法检测p53、p21WAF/CIP1及MDM2蛋白的表达,采用统计学分析它们的表达及其与临床病理参数之间的关系.结果p53、p21WAF/CIP1及MDM2在HCC组织中的阳性表达率分别为83.5%(96/115)、36.5%(42/115)和48.7%(56/115),同癌旁组织相比,p53、p21WAF/CIP1及MDM2的表达均明显增高,P＜0.05.两两相关分析比较, p53表达分别与p21WAF/CIP1和MDM2表达有关;p53、p21WAF/CIP1及MDM2的阳性表达率与患者性别、年龄、肿瘤大小、肿瘤数量、HBsAg、病理分级、血清AFP浓度和患者生存时间均无关,P均＞0.05.结论p53、p21WAF/CIP1及MDM2在HCC组织中呈增高表达并具有一定的相关性,提示它们可能在HCC的发生发展中发挥重要的作用.     

p27~(Kip1)和细胞周期蛋白D1在胃癌中的表达及其预后意义

目的 :研究p2 7Kip1、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p2 7Kip1、cyclinD1蛋白的表达水平。结果 :本组 92例胃癌中 ,p2 7Kip1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 ,p2 7Kip1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 .0 5 ) ;cyclinD1蛋白表达与病理组织学分级负相关 (P <0 .0 5 ) ;p2 7Kip1与cyclinD1蛋白阳性表达显著相关 (P <0 .0 5 ) ;单变量生存分析结果 ,p2 7Kip1高表达组三年、五年生存率分别为 77.1%、5 7.8% ,明显高于低表达组的 33.7%、2 6 .3 % (P =0 .0 0 7) ,多变量分析显示p2 7Kip1是一个独立的预后指标 (P =0 .0 0 0 3)。结论 :p2 7Kip1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 ;cyclinD1是胃癌发生、发展过程中早期的分子事件 ;p2 7Kip1在胃癌进展中起着比cyclinD1更重要的作用。     

胰腺癌中p21WAF1、cyclinD1和CDK4的表达意义及其相互关系

目的:探讨胰腺癌中p21WAF1、cyclinD1和CDK4的表达意义及其相互关系.方法:应用免疫组织化学二步法检测p21WAF1、cyclinD1和CDK4在48例胰腺癌和14例慢性胰腺炎中的表达.结果:胰腺癌组织中p21WAF1、cyclinD1、CDK4的阳性表达率分别是52.08%(25/48)、70.85%(34/48)、62.50%(30/48),同慢性胰腺炎组比较p21WAF1的表达明显降低(P＜0.01),而cyclinD1和CDK4的表达明显升高(P＜0.01).高分化、无淋巴结转移、临床分期Ⅰ、Ⅱ期的胰腺癌组织中p21WAF1的阳性表达率明显高于低分化、有淋巴结转移、临床分期Ⅲ、Ⅳ期的胰腺癌(P＜0.05);而cyclinD1和CDK4则相反(P＜0.05).p21WAF1的表达和cyclinD1、CDK4的表达呈明显的负相关(相关系数分别为r=-0.340,P＜0.05和r=-0.571,P＜0.01);cvclinD1和CDK4的表达则呈明显的正相关(r=0.450,P＜0.01).结论:p21WAF1的缺失表达和cyclinD1、CDK4的过表达在胰腺癌的发生、发展过程中起重要的协同作用.三种蛋白质主要以p21WAF1/cyclinD1/CDK4通路的方式作用于细胞的转化,参与肿瘤的形成.     

胃癌及癌前病变中p16、p21WAF1、CDK4、cyclin D1蛋白的表达及其意义

目的探讨胃癌及癌前病变中p16、p21WAF1、CDK4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、p21WAF1、CDK4和cyclinD1蛋白的表达情况。结果胃癌中p16和p21WAF1蛋白表达率分别为52.7％、30.9％,显著低于慢性浅表性胃炎和不典型增生（P<0.01）,而CDK4和cyclinD1蛋白表达率分别为61.8％、47.3％,均明显高于正常胃组织和慢性浅表性胃炎,差异有显著性（P<0.01）,但胃癌和不典型增生组织中CDK4和cyclinD1蛋白表达率之间差异无显著性（P>0.05）。胃癌中p16与cyclinD1蛋白表达呈负相关关系（P<0.05）,而CDK4与cyclinD1呈正相关关系（P<0.01）。结论胃癌发生机制涉及p16、p21WAF1、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cyclinD1蛋白高表达可能是胃癌发生过程中的早期分子事件。     

Patterns of cyclin E, retinoblastoma protein, and p21Cip1/WAF1 immunostaining in the oncogenesis of papillary thyroid carcinoma.

PURPOSE: Uncontrolled cell proliferation, a hallmark of cancer, may result from an increased expression of cell cycle up-regulators, and/or from a reduced expression of cell cycle down-regulators. In the present study, we analyzed, by immunohistochemistry, the expression of a panel of three proteins: cyclin E and two cell cycle inhibitors, p21(Cip1/WAF1) and retinoblastoma protein (pRb) product, in different stages of papillary thyroid carcinomas (PTC). EXPERIMENTAL DESIGN: We investigated immunostaining patterns of the proteins in question in 51 resected PTC in pathologic stages, ranging from pT(1a) to pT(4), taking into consideration their relation to clinicohistopathologic factors. RESULTS: We observed a significant, progressive loss of expression of p21(Cip1/WAF1) with advancing tumor grade. The differences reached values of significance between pT(1a) [papillary thyroid microcarcinomas (PMC)] and pT(2) and between PMC and pT(4) stages of PTC. pRb presented a similar immunostaining pattern to that of p21(Cip1/WAF1) and the differences reached values of significance between pT(1a) and pT(2), and between PMC and pT(4) stages of PTC. The results of cyclin E immunostaining corresponded to our recently published result, and a negative correlation was observed between the immunostaining index of cyclin E and pRb. CONCLUSIONS: The results of the present study suggest that cyclin E expression and suppression of pRb and p21(Cip1/WAF1) may be characteristic patterns of immunostaining for PTC with a tendency to early metastasizing. If our results are confirmed in a larger study, the diagnostic panel, constructed of the antibodies against these proteins, may become a valuable tool in predicting the metastatic potential in PTC.     

p21 is associated with cyclin D1, p16INK4a and pRb expression in resectable non-small cell lung cancer

p21 (p21WAF1/CIP1) is involved in cell cycle regulation, as an inhibitor of cyclin dependent kinases (CDK2, CDK4 and CDK6). However, subsequent in vitro studies have suggested that p21 may influence this process by an additional mechanism, in particular through the regulation of cyclin D1 subcellular localisation. This study of primary resectable non-small cell lung cancer (NSCLC) was designed to examine p21 functions in association with the expression of cyclin D1 (including its subcellular localisation), p16INK4a and pRb. p21 expression was examined in 50 NSCLC (stage I-IIIA) and in several normal lung samples all of which had previously been studied for cyclin D1 (DNA, RT-PCR, immunostaining), p16INK4a (DNA, RT-PCR, immunostaining), and pRb (immunostaining). As assessed by immunoblotting and immunostaining, p21 was expressed at low levels in normal lung tissue with immunoreactivity seen in a small number of bronchial epithelial cells only. In NSCLC, p21 expression (> or =10% of positive cells) was observed in 42% (21/50) of cases. High p21 expression was associated with well differentiated tumours (p = 0.01) and cyclin D1 nuclear staining (p = 0.02). Furthermore, we found an inverse correlation with p16INK4a (p = 0.004) and a direct correlation with pRb expression (p = 0.02). Risk of relapse was associated with p16INK4a and p21 status with no relapse in patients with normal p16INK4a and p21. Our results confirm that a large number of NSCLC have a low level of p21 expression. The associations of p21 and nuclear cyclin D1, pRb, p16INK4a support the relevance of pathways linked to lung carcinogenesis that involve p21 but may act in addition to direct CDK inhibition.     

Expression of cell-cycle regulators, cyclin E and p21WAF1/CIP1, potential prognostic markers for gastric cancer.

AIMS: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. METHODS: In this study, we analysed the expression of cyclin D1, cyclin E, p21WAF1/CIP1 and p27KIP1 in 84 surgically resected gastric cancers by immunohistochemistry with long-term follow-up (median 38 months). We also evaluated the relation between each cell cycle regulator and various clinicopathological findings, including age, sex, histological grade, tumour location, tumour type and stage and lymph-node metastasis. RESULTS: Overexpression of cyclin D1 and E was detected in 21/84 (25%) and 34/84 (40.5%) patients, respectively. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1 and p27KIP1 in more than 50% of nuclei. Loss of p21WAF1/CIP1 and p27KIP1 expression was noted in 45/84 (53.6%) and 44/84 (52.4%) patients, respectively. Among the various clinicopathological findings, overexpression of cyclin E was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.043). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.002). Overexpression of cyclin E and loss of p21WAF1/CIP1 expression were significantly correlated with decreased disease-free (P=0.037; P= 0.001) and overall (P=0.031; P=0.001) survival. CONCLUSIONS: These results suggest that immunohistochemical analysis for cell cycle regulators, especially cyclin E and p21WAF1/CIP1, might be a useful prognostic indicator in gastric cancer.     

Retinoblastoma Gene Product and P21 (WAF1, CIP1) Protein Expression in Non Hodgkin's Lymphomas: A Multivariate Survival Analysis

We evaluated immunohistochemically the expression of two negative regulators of the cell cycle, namely retinoblastoma gene product (pRb) and WAF1/Cip1 gene product (p21), in paraffin sections from 93 patients with non-Hodgkin's lymphomas (NHL) and related it to clinicopathological parameters, proliferative fraction, p53 expression and survival. Patients were followed until death (n=33) or for an average of 52 months (60-160). Rb labelling index (LI) increased with malignancy grade and proliferative activity but was unrelated to other clinicopathological parameters. In 33% of cases, especially those of the aggressive groups, we observed diminished pRb expression (i.e. low pRb/Ki-67 ratio). p21 expression on the other hand correlated only with histological grade, Rb LI and p53 LI. In multivariate analysis, Rb LI was a negative predictor of disease-free survival but was linked to a higher probability of complete response. However, diminished pRb expression as well as p21 expression were not statistically significant prognostic indicators. Our results suggest that pRb as a cell cycle related molecule may play an important role in determining prognosis and therapeutic response in NHL patients.     

Retinoblastoma gene product and P21 (WAF1, CIP1) protein expression in non Hodgkin's lymphomas: a multivariate survival analysis.

We evaluated immunohistochemically the expression of two negative regulators of the cell cycle, namely retinoblastoma gene product (pRb) and WAF1/Cip1 gene product (p21), in paraffin sections from 93 patients with non-Hodgkin's lymphomas (NHL) and related it to clinicopathological parameters, proliferative fraction, p53 expression and survival. Patients were followed until death (n=33) or for an average of 52 months (60-160). Rb labelling index (LI) increased with malignancy grade and proliferative activity but was unrelated to other clinicopathological parameters. In 33% of cases, especially those of the aggressive groups, we observed diminished pRb expression (i.e. low pRb/Ki-67 ratio). p21 expression on the other hand correlated only with histological grade, Rb LI and p53 LI. In multivariate analysis, Rb LI was a negative predictor of disease-free survival but was linked to a higher probability of complete response. However, diminished pRb expression as well as p21 expression were not statistically significant prognostic indicators. Our results suggest that pRb as a cell cycle related molecule may play an important role in determining prognosis and therapeutic response in NHL patients.     

Aberrant expression of G(1)/S regulators is a frequent event in sporadic pituitary adenomas

Components of the pRb/p16/cyclin D1/CDK4 pathway are frequent targets in numerous tumour types, including those of pituitary origin. However, previous studies of pituitary tumours have examined individual components of this pathway. Therefore, to determine their overall contribution we have simultaneously examined the immunohistochemical status of pRb, p16 and cyclin D1 and analysed the CDK4 gene for a characterized activating mutation. Of the total pituitary tumour cohort (29 clinically non-functioning adenomas and 16 somatotrophinomas) abnormal expression of either pRb, p16 or cyclin D1 was observed in 36 of 45 (80%) tumours and was significantly (P = 0.005) associated with non-functioning tumours (27/29; 93%) compared with somatotrophinomas (9/16, 56%). Loss of either pRb or p16 expression was mutually exclusive in 23 of 45 (51%) tumours, whilst concomitant loss of pRb and p16 expression was observed in five tumours. Cyclin D1 overexpression was observed in 22 of 45 (49%) tumours, however, there was no significant association between overexpression of cyclin D1 and the expression status of either pRb or p16. In addition, no activating mutations within codon 24 of the CDK4 gene were detected. This study provides evidence for the first time that components of the pRb/p16/cyclin D1/CDK4 pathway, either alone or in combination, are frequently deregulated in human pituitary tumours, suggesting that this pathway may be a useful target in drug or gene therapeutic approaches.     

Cyclin E和p27~(kip1)在膀胱移行细胞癌中的表达及其意义

目的　探讨CyclinE和p2 7kip1在膀胱移行细胞癌 (BTCC)中的表达 ,并评价其相关性和意义。方法　应用鼠抗人CyclinE和 p2 7kip1单克隆抗体对 65例BTCC和 12例正常粘膜进行免疫组化SP法染色。结果　CyclinE在BTCC中阳性表达率随着病理分级 (P <0 .0 5 )和临床分期 (P <0 .0 1)的升高而增高 ,有淋巴结转移组非常显著高于无淋巴结转移组 (P <0 .0 1) ;而p2 7kip1在BTCC中的阳性表达率随着临床分期和病理分级的增高而降低 (P <0 .0 5 ) ,有淋巴结转移组显著低于无淋巴结转移组 (P <0 .0 5 )。CyclinE和 p2 7kip1在BTCC中表达具有负相关性 (r =-0 .2 62 ,P <0 .0 5 )。结论　CyclinE对BTCC的分化、增殖、浸润和转移可能起促进作用 ;而p2 7kip1则对BTCC的分化、增殖、浸润和转移可能起抑制作用 :两者在细胞周期进展中的共同表达失调 ,可能是导致BTCC发生发展和向恶性表型转化的机制之一。     

Cyclin D1, p53, and p21Waf1/Cip1 expression is predictive of poor clinical outcome in serous epithelial ovarian cancer.

PURPOSE: Dysregulation of cell cycle control, in particular G(1)-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear. EXPERIMENTAL DESIGN: The expression of selected genes from the pRb pathway that regulates G(1)-S-phase progression, including cyclin D1, p16(Ink4a), cyclin E, p27(Kip1), p21(Waf1/Cip1), and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome. RESULTS: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27(Kip1) (P = 0.05) and p21(Waf1/Cip1) (P = 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21(Waf1/Cip1) had a significantly shorter overall (P = 0.0008) and progression-free survival (P = 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21(Waf1/Cip1) in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21(Waf1/Cip1) loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27(Kip1) and p21(Waf1/Cip1) were significantly associated with increasing tumor grade. CONCLUSIONS: This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC.     

人非小细胞肺癌组织中survivin,caspase-3及P21WAF1的表达意义

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中survivin,caspase-3和p21WAF1的蛋白表达与临床病理指标的关系以及survivin与caspase-3和p21WAF1蛋白表达之间的关系.方法在57例NSCLC原发灶中应用免疫组织化学S-P法检测survivin,caspase-3和p21WAF1蛋白的表达.结果在57例NSCLC原发灶中survivin,caspase-3和p21WAF1 3种蛋白表达阳性率分别为71.93%,66.67%,49.12%.它们均与组织学类型无关(P＞0.05),而与淋巴结转移均有显著性相关(P＜0.05);survivin,caspase-3蛋白的表达与肿瘤细胞分化程度无关(P＞0.05),但p21WAF1与肿瘤细胞分化程度显著相关(P=0.018).57例NSCLC中,survivin的表达与caspase-3,p21WAF1均呈显著负相关(P=0.001及P=0.000).结论survivin,caspase-3和p21WAF1均与NSCLC的浸润进展显著相关.survivin可能直接作用于caspase-3,阻断了细胞的凋亡过程,或通过抑制p21WAF1的表达而缩短了细胞周期,从而促进了NSCLC的癌细胞不断增生.