Cyclin D1蛋白表达与卵巢癌转移相关性研究

目的:探讨细胞周期蛋白(CyclinD1)表达与卵巢癌转移的相关性和CyclinD1与P21WAF1、P53蛋白的关系。方法:应用蛋白免疫印迹技术(Westernblot)检测61例人卵巢癌组织及7例卵巢非癌组织中CyclinD1、P53及P21WAF1蛋白的表达。结果:卵巢癌组织中CyclinD1和P53蛋白表达率均明显高于卵巢非癌组织(P<0.05);P21WAF1蛋白表达卵巢癌组织低于卵巢非癌组织(P>0.05)。CyclinD1与P53及P21WAF1蛋白表达与卵巢癌组织类型无关(P>0.05)。P21WAF1蛋白表达与卵巢癌的临床分期相关(P<0.05),CyclinD1、P53蛋白表达与卵巢癌的临床分期无关(P>0.05)。CyclinD1、P53及P21WAF1蛋白表达与卵巢癌转移相关(P<0.05)。结论:CyclinD1蛋白表达与卵巢癌肿瘤转移相关,CyclinD1与P21WAF1、P53蛋白在卵巢癌发生、发展中可能有一定作用,但不起协同作用。     

子宫颈癌中Plk1和Cyclin B1、p21 WAF1的表达及其临床意义

目的：探讨Plk1(polo-like kinase1)和Cyclin B1、p21WAF1在子宫颈癌中的表达及其与临床病理因素之间的关系。方法利用组织芯片技术,结合免疫组化EliVision 法对102例子宫颈癌、20例子宫颈上皮内瘤变(cervical intraepithelial neoplasia, CIN)、20例正常子宫颈组织中Plk1和Cyclin B1、p21WAF1的表达进行检测,并分析相关数据。结果 Plk1在子宫颈癌、CIN 中的阳性率分别为70．5%、55．0%,明显高于正常子宫颈组织(10%),差异有统计学意义(P <0．01)。Cyclin B1在子宫颈癌、 CIN 中的阳性率分别为52．9%,30．0%,明显高于正常子宫颈组织(10．0%),差异有统计学意义(P <0．01)。p21WAF1在子宫颈癌、CIN 中的阳性率分别为23．5%、10．0%,明显高于正常子宫颈组织(0),差异有统计学意义(P <0．05)。Plk1、Cyclin B1和 p21WAF1在子宫颈癌、CIN 中的表达差异均无统计学意义(P >0．05)。Plk1表达与子宫颈癌间质浸润深度相关(P <0．05)。Cyclin B1表达与子宫颈癌间质浸润深度及淋巴结转移相关(P <0．05)。p21WAF1在子宫颈癌中的表达与组织学分级相关(P <0．01)。组织学分级低的子宫颈癌中p21WAF1阳性率高。Plk1和Cyclin B1在子宫颈癌中的表达呈正相关(rs =0．297,P =0．002)。Plk1和p21WAF1在子宫颈癌中的表达呈负相关(rs =-0．403,P <0．001)。结论 Plk1、Cyclin B1和p21WAF1的表达与子宫颈癌的发生、发展相关,且前两者与子宫颈癌预后相关,三者联合检测有可能成为子宫颈癌临床治疗的新靶点。     

胃癌组织中AEG-1、Cyclin D1的表达及其意义

目的 观察胃癌组织中星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)、Cyclin D1的表达,分析二者表达与胃癌侵袭、转移的关系.方法 应用免疫组化EnVision法检测110例胃癌组织中AEG-1和Cyclin D1的表达,并复习相关文献.结果 AEG-1在胃癌组织中的阳性率为69.1％,AEG-1表达与癌组织Lauren分型、淋巴结转移、浸润深度和pTNM分期密切相关(P＜0.05),与患者性别、年龄、发生部位和肿瘤大小无关(P ＞0.05);Cyclin D1在胃癌组织中的阳性率为57.3％,Cyclin D1表达与癌组织浸润深度、淋巴结转移和pTNM分期有关(P＜0.05),与患者性别、年龄、发生部位、肿瘤大小和Lauren分型无关(P＞0.05).相关性分析显示,胃癌组织中AEG-1与Cyclin D1的表达呈正相关(P＜0.05).结论 AEG-1可能通过上调Cy-clin D1的表达而促进胃癌细胞的侵袭、转移.AEG-1可能作为胃癌治疗的一种潜在分子靶点.     

上皮性卵巢癌中Cyclin D1和p27的表达及其临床意义

目的探讨Cyclin D1和p27蛋白在上皮性卵巢癌中的表达及其与临床病理间的关系。方法利用免疫组化S-P法测定Cyclin D1和p27蛋白在62例上皮性卵巢癌中的表达,比较Cyclin D1、p27蛋白与卵巢癌的各项临床病理指标间的关系及两者间的关系。结果在上皮性卵巢癌中,Cyclin D1蛋白的表达在FIGO分期Ⅰ-Ⅱ期低于Ⅲ-Ⅳ期,组织学G1-G2组低于G3组,术后残留癌组织≤2cm组低于〉2cm组,淋巴无转移组低于有转移组;而p27蛋白在FIGO分期Ⅰ-Ⅱ期高于Ⅲ-Ⅳ期,组织学G1-G2组高于G3组,淋巴无转移组高于有转移组,以上各组间均有统计学差异（P〈0.05）;在上皮性卵巢癌中Cyclin Dl、p27蛋白的表达呈负相关（rs=-0.255,P〈0.05）。结论CyclinDl、p27蛋白的异常表达可能与上皮性卵巢癌的发展及恶性程度有关,可作为评估上皮性卵巢癌恶性程度和预后的指标。     

卵巢癌组织中Cyclin E和Cyclin D表达水平特征及临床意义

目的 探讨细胞周期调节蛋白cyclin E和cyclin D蛋白在卵巢癌组织中的表达情况,及其与病理特征相关性.方法 采用免疫组化法检测40例正常卵巢组织、20例良性卵巢上皮肿瘤组织和40例卵巢癌组织中cyclin E和cyclin D蛋白表达水平,并与病理资料进行交叉比较.结果 cyclin E和cyclin D蛋白在卵巢癌组织、良性组织和正常组织中表达率均呈显著下降趋势(X2=26.813,X2=18.742,P＜0.05).卵巢癌组织中cyclin D蛋白阳性率随组织分级升高、淋巴转移而增高(X2=8.189,X2=14.115,P＜0.05).cyclin E蛋白随阳性率随手术病理分期、组织分级升高、淋巴转移而增高(X2=13.190,X2 =4.682,X2=9.122,P＜0.05).cyclin E和cyclin D表达正相关(r=0.038,P＜0.01).结论 cyclin E和cyclinD均参与了卵巢癌的发生,且与卵巢癌的发展具有相关性并可能起到了协同作用.     

Cyclin D1和p16、p27在脑胶质瘤中的表达及其与PCNA的相关性

目的检测Cyclin D1和p16、p27以及PCNA在脑胶质瘤中的表达状况,以探讨不同病理类型脑胶质瘤中各自的表达及其相关性.方法应用免疫组化S-P法,检测12例正常脑组织、58例脑胶质瘤组织中Cyclin D1、p16、p27及PCNA表达及其特征.结果Cyclin D1在由低度恶性胶质瘤向高度恶性胶质瘤转化中阳性表达逐渐增强(χ2检验,P＜0.005,χ2=51.67);而p16、p27阳性表达却是随着胶质瘤恶性程度的升高而降低(χ2检验,P值均＜0.005,χ2分别为15.41和12.81).Cyclin D1与PCNA呈正相关,rs=0.745;p16和p27与PCNA呈负相关,rs分别为-0.566和-0.612.结论脑胶质瘤中Cyclin D1的表达程度对胶质瘤的细胞增殖活性起促进作用,而p16、p27的表达则起抑制作用.     

Cyclin D1和p16、p27在脑胶质瘤中的表达及其与PCNA的相关性

目的 :检测CyclinD1 和p16、p2 7以及PCNA在脑胶质瘤中的表达状况 ,以探讨不同病理类型脑胶质瘤中各自的表达及其相关性。方法 :应用免疫组化S P法 ,检测 12例正常脑组织、5 8例脑胶质瘤组织中CyclinD1 、p16、p2 7及PCNA表达及其特征。结果 :CyclinD1 在由低度恶性胶质瘤向高度恶性胶质瘤转化中阳性表达逐渐增强 (χ2 检验 ,P <0 0 0 5 ,χ2 =5 1 6 7) ;而p16、p2 7阳性表达却是随着胶质瘤恶性程度的升高而降低 (χ2 检验 ,P值均 <0 0 0 5 ,χ2 分别为 15 4 1和 12 81)。CyclinD1 与PCNA呈正相关 ,rs =0 74 5 ;p16和p2 7与PCNA呈负相关 ,rs分别为 - 0 5 6 6和 - 0 6 12。结论 :脑胶质瘤中CyclinD1的表达程度对胶质瘤的细胞增殖活性起促进作用 ,而p16、p2 7的表达则起抑制作用。     

人子宫内膜癌中p57 kip2、Cyclin D1的表达及意义

目的：探讨p57 kip2、Cyclin D1在人子宫内膜癌发生、发展中的作用。方法选取子宫内膜样腺癌( endometrioid adenocar-cinoma, EA)100例、子宫内膜上皮内瘤变(endometrial intraepithelial neoplasia, EIN)20例、子宫内膜增生性病变20例、增生期子宫内膜组织20例;选取不同子宫内膜细胞[高分化子宫内膜癌细胞( Ishikawa)、中分化子宫内膜癌细胞( JEC)、低分化子宫内膜癌细胞(KLE)及正常子宫内膜细胞(ESC)]进行细胞培养。应用免疫组化EliVision法检测不同子宫内膜组织中p57kip2、Cyclin D1蛋白的表达;Western blot法检测不同子宫内膜细胞中p57 kip2、Cyclin D1蛋白的表达。结果 p57 kip2蛋白在EIN组织中表达最高,在增生期子宫内膜、EA、子宫内膜增生性病变组织中表达逐渐降低,子宫内膜增生性病变与EIN组织中p57 kip2蛋白表达差异有统计学意义(P<0.05)。 Cyclin D1蛋白在EA组织中表达最高,在增生期子宫内膜组织中表达最低,在子宫内膜增生性病变组织、EIN组织中表达依次增高,差异均有显著性( P<0.01)。 p57 kip2、Cyclin D1蛋白在EA组织中的表达随着组织学分级的增高呈依次递减趋势,但仅p57 kip2蛋白表达和组织学分级有关( P<0.05)。 p57 kip2蛋白在KLE中表达最高,在ESC中表达最低,两组相比差异有显著性( P<0.05);Cyclin D1在JEC、Ishikawa中的表达高于ESC,差异均有显著性( P<0.05)。结论 p57kip2、Cyclin D1均参与子宫内膜癌的发生、发展。 Cyclin D1表达是子宫内膜癌发生的早期事件,可能还存在异常合成的p57 kip2蛋白,其协同Cyclin D1促进子宫内膜的恶性转化。联合检测p57 kip2、Cyclin D1在子宫内膜癌中的表达,对预测子宫内膜癌患者预后有一定的临床意义。     

子宫颈鳞状细胞癌中DLC-1和Cyclin D1的表达及其相关性分析

目的 观察肝癌缺失基因-1(deleted in liver cancer-1,DLC-1)和Cyclin D1在正常子宫颈组织、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及子宫颈鳞状细胞癌(cervical squamous cell carcinoma,CSCC)中的表达,并探讨二者与CSCC临床病理参数间的关系.方法 应用免疫组化SP法及逆转录-聚合酶链反应法(RT-PCR)检测DLC-1和Cyclin D1在正常子宫颈组织、CIN及CSCC中的表达,采用统计学软件SPSS 19.0对数据进行分析.结果 (1)DLC-1在正常子宫颈组织、CIN及CSCC中的阳性率依次降低,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,结合RT-PCR结果,差异具有统计学意义(P＜0.05);(2) Cyclin D1在正常子宫颈组织、CIN和CSCC中的阳性率依次升高,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,结合RT-PCR结果,差异具有统计学意义(P ＜0.05);(3) DLC-1和Cyclin D1在CSCC中的表达呈负相关(r=-0.526,P＜0.001).结论 DLC-1低表达和Cyclin D1高表达与CSCC的发生、发展和侵袭、转移相关,二者联合检测可作为CSCC诊断、治疗的重要判断指标.     

Cyclin D3与Ki67在非霍奇金淋巴瘤中的表达及其意义

目的：探讨cyclinD3和Ki67在我国非霍奇金淋巴瘤(non-Hodgidn’s lymphoma，NHL）中的表达及其意义。方法：采用免疫组织化学方法检测114例IXTIL和20例反应性增生淋巴结中cyclinD3及Ki67的表达情况。结果：cyclin D3在反应性增生淋巴结(不包括生发中心)中的阳性率明显低于NHL。随着肿瘤侵袭性的增加，cyclinD3表达水平升高。Ki67在反应性增生淋巴结和NHL中的表达情况与cyclin D3一致。NHL中cyclinD3的阳性率与Ki67的表达水平呈明显正相关。结论：cyclinD3和Ki67的表达与NHL的细胞增殖活性和恶性程度密切相关，提示cyclin D3在淋巴瘤的恶性增殖过程中发挥重要作用，为淋巴瘤的诊治提供新的依据和靶点。     

皮肤瘢痕及瘢痕癌组织中cyclin A、p21WAF1的表达及意义

目的 探讨cyclin A、p21WAF1在皮肤病理性瘢痕和瘢痕癌组织中的表达及意义.方法 以病理性皮肤瘢痕、皮肤瘢痕癌组织为研究对象,以正常皮肤组织为对照.采用免疫组化SP法分别检测cyclin A、p21WAF1蛋白的表达,采用核酸分子原位杂交法检测cyclin A mRNA、p21WAF1 mRNA的表达,结合图像分析,分别观测3组被检组织中所检各项指标的表达(平均光密度和阳性面积);所有数据输入计算机后运用SPSS 16.0软件包进行统计学分析.结果 (1)cyclin A、cyclin A mRNA在正常皮肤表皮和病理性皮肤瘢痕上皮中的表达呈阴性或弱阳性,在瘢痕癌组织中呈强阳性.瘢痕癌组的表达(平均光密度和阳性面积)与正常皮肤组及皮肤瘢痕组比较,差异均有统计学意义(P＜0.01),但正常皮肤组与瘢痕组比较,差异无统计学意义(P＞0.05).(2)p21WAF1蛋白、p21WAF1 mRNA在正常皮肤表皮和病理性皮肤瘢痕上皮中的表达呈阴性或弱阳性,在瘢痕癌组织中呈强阳性.瘢痕癌组的表达(平均光密度和阳性面积)与正常皮肤组及皮肤瘢痕组比较,差异均有统计学意义(P<0.01),但正常皮肤组与瘢痕组比较,差异无统计学意义(P>0.05).(3)相关分析显示,在皮肤瘢痕癌中,cyclin A 与cyclin A mRNA(r=0.766,P<0.01)、p21WAF1与p21WAF1 mRNA(r=0.791,P<0.01)的表达呈正相关;cyclin A与p21WAF1蛋白(r=0.656,P<0.01)的表达呈正相关;cyclin A mRNA与p21WAF1 mRNA的表达呈正相关(r=0.475,P<0.05).结论 (1)cyclin A及其mRNA的高表达,可能与皮肤瘢痕癌的发生有关;(2)在瘢痕癌中,cyclin A、p21WAF1同时存在蛋白水平和基因水平的异常表达;(3)p21WAF1及其mRNA在瘢痕癌中的高表达可能与细胞周期调控的反馈机制有关.     

An Immunohistochemical Analysis of Cyclin D1, p53, and p21 Proteins in Tumors Originating fromthe Follicular Epithelium of the Thyroid Gland*

This study aimed at clarifying the factors closely related to the tumor progression of thyroid neoplasms. We examined the immunoreactivity of cyclin D1, p53, and p21^waf1/cip1 proteins in 179 thyroid tumors originating from the follicular epithelium using an immunohistochemical technique. Cyclin D1 positivity was frequent in well-differentiated thyroid carcinomas (39/122 cases), but it was rarely seen in follicular adenomas (1/33 cases), (p < 0.05). Positivity for p53 was more frequent in poorly differentiated carcinomas (7/19 cases) and undifferentiated carcinomas (4/5 cases) than in well-differentiated carcinomas (14/122 cases) (p < 0,05, respectively). P21^wafl/cip1 positivity was more frequent in well-differentiated thyroid carcinomas (43/122 cases) than in follicular adenomas (4/33 cases) (p < 0.05). Regarding the relationships of these proteins, co-positivity for cyclin D1 and p53 was observed more often in poorly differentiated carcinomas (5/7 cases) than in well-differentiated carcinomas (7/39 cases) (p < 0.05). Most cases with cyclin D1 positivity did not show p21^waf1/cip1 expression in poorly differentiated carcinomas (6/7 cases). Three cases examined showed co-positivity of p53 and p21^waf1/cip1.Our results suggest that cyclin D1 is invoved in thyroid oncogenesis. Moreover, p53 might be closely related to the development of poorly differentiated carcinomas and undifferentiated carcinomas originating from well-differentiated carcinomas.     

前列腺癌p21CIP1/WAF1、Rb及PCNA的表达及意义

目的研究p21^CIP1/WAF1、Rb及PCNA在人前列腺癌标本中的表达及三者相关性,阐述它们与前列腺癌病理分级及临床分期的关系。方法收集36例确诊前列腺癌石蜡包埋存档标本作为研究对象,采用免疫组化SABC法对其p21^CIP1/WAF1、Rb及PCNA进行检测,并应用图象分析仪判定,统计学处理,对前列腺癌的病理分级及临床分期进行了对比分析及相关性研究。结果p21^CIP1/WAF1、Rb及PCNA的免疫组化阳性染色为棕黄色和／或棕褐色,定位于细胞浆或细胞核。所得数据均经统计学处理。在不同病理分级、临床分期之间差异均有显著性,同时还发现PCNA与p21^CIP1/WAF1及Rb之间存在显著负相关性。但未发现p21^CIP1/WAF1、与Rb有显著相关性。结论p21^CIP1/WAF1、Rb表达与前列腺癌组织的病理分级、临床分期呈负相关性,在发病机制中可能涉及到p21^CIP1/WAF1、Rb和PCNA凋节通路的异常。同时,作为一种检测方法,可用于判定前列腺癌恶性程度及进程的有价值的指标,对诊治康复也可提供有意义的帮助。     

Expression of p21/WAF-1, status of apoptosis and p53 mutation in esophageal squamous cell carcinoma with HPV infection

Human papilloma virus (HPV) is regarded as a causative carcinogenic agent in anogenital squamous cell carcinoma (SCC), but there is controversy about its etiologic role in esophageal SCC (ESCC). In this study, we attempted to clarify whether HPV infection plays a crucial role in the development of ESCC by analysis of multiple factors. These included: detection of HPV DNA; evaluation of immunohistochemical assays for HPV-related cell cycle regulators and apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method; and genetic analysis of the p53 gene. Twenty of the 48 ESCC examined (42%) were found to be positive for the HPV genome by polymerase chain reaction. They comprised 16 cases with the HPV16 subtype, three with the HPV18 subtype, and one with both HPV16 and 18. Immunohistochemical analysis revealed that the expression of p21/WAF-1 was significantly decreased in HPV-positive cases (chi2 = 9.2614; P = 0.0023). Furthermore, the 10 apoptosis-negative (< or =10%) cases of HPV-positive SCC were almost exclusively p21/WAF-1-negative (chi2 = 12.1406; P = 0.0005), indicating the significance of the relationship between HPV infection and the phenotype that is expected from HPV-induced inhibition of p53. Although 14 cases possessed missense and deletion mutations of the p53 gene (of which four mutations were found in HPV-positive ESCC), no accumulation of the mutation was defined in the phenotype, suggesting that distinct mutation processes might be involved in HPV-negative and -positive ESCC. The data provide significant support for the hypothesis that HPV infection may play a crucial role in the oncogenesis of some ESCC.     

Cyclin D1 and p21 in ulcerative colitis-related inflammation and epithelial neoplasia: a study of aberrant expression and underlying mechanisms

It is unclear whether and how cyclin D1 and/or p21(WAF1/CIP1) dysregulation contribute to ulcerative colitis (UC)-related inflammation and colorectal carcinogenesis. Cases of quiescent UC (QUC; n = 15), active UC (AUC; n = 23), UC-related dysplasia (n = 35) and UC-related colorectal adenocarcinomas (CRCs; n = 11) were studied with cyclin D1 and p21(WAF1/CIP1) immunohistochemistry. The CRCs were also studied with beta-catenin, bcl2, and p53 immunohistochemistry, p53 and k-ras mutation analyses, and cyclin D1 gene fluorescence in situ hybridization. QUC showed cyclin D1 (negative/weak staining) and p21(WAF1/CIP1) (surface epithelial and upper-third crypt staining) expression similar to that of normal colorectum. Moderate or strong cyclin D1 immunostaining was seen in 9% of AUC cases, 40% of dysplasia cases, and 36% of UC-related CRCs. Although these carcinomas showed neither cyclin D1 gene amplification nor any association between k-ras mutation and cyclin D1 overexpression, the latter was closely related to nuclear beta-catenin expression. Increased lower-third crypt p21(WAF1/CIP1) staining was seen in 57% of AUC cases; decreased upper-third crypt p21(WAF1/CIP1) staining, in 23% of dysplasia cases; and absent or weak p21(WAF1/CIP1) staining, in 55% of UC-related CRCs. The latter change was always associated with p53 mutation but could not be related to p53 or bcl2 expression. In conclusion, AUC shows up-regulated cyclin D1 and p21(WAF1/CIP1) expression. Cyclin D1 up-regulation and p21(WAF1/CIP1) down-regulation occur early in UC-related carcinogenesis. Cyclin D1 up-regulation is less common in UC-related CRCs than in sporadic CRCs, and is related to beta-catenin nuclear signaling. p21(WAF1/CIP1) down-regulation is seen at an equal or higher frequency among UC-related CRCs compared with sporadic CRCs and is attributable to p53 mutation.     

Cyclin D1 expression in prostate carcinoma

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.