细胞周期蛋白cyclin D1、CDK4在食管癌中的表达及其意义

目的：获得食管癌发生过程中调节Ｇ１细胞周期各种因子的作用。方法：采用抗ｃｙｃｌｉｎＤ１和ＣＤＫ４的单克隆抗体对１０例下沉食管和５０例食管鳞状上皮癌标本进行免疫组织化学染色。结果：ｃｙｃｌｉｎＤ１和ＣＤＫ４在正常食管上皮呈现较低水平的表达,在食管鳞状上皮癌中则过表达。２７／５０食管鳞状上皮癌ｙｃｙｃｌｉｎＤ１染色阳性,其中８例强阳性,１２例只表达ＣＤＫ４,１１例只表达ｃｙｃｌｉｎＤ１,１４例既表达ｃ     

细胞周期相关蛋白CyclinD1、CDK4、p16在大肠癌中的表达及其意义

目的 探讨细胞周期调控因子在大肠癌中的表达及其与大肠癌临床病理特征的关系.方法 应用免疫组化S-P法对70例大肠癌组织及距癌灶3 cm以外的癌旁组织,10 cm以外的正常组织中CyclinD1、CDK4、和p16进行检测.结果 CyelinD1和CDK4在大肠癌中过度表达,分别为36/70(51.4%)和28/70(40.0%),并与肿瘤的分化程度呈反比,有淋巴结转移的大肠癌,其CyclinD1和CDK4的阳性率分别为70.0%和60.0%,无淋巴结转移的大肠癌阳性率分别为44.0%和32.0%,两者相比差异有显著性(P《0.05),p16在大肠癌中为低表达33/70(47.1%),癌旁组织和正常组织中p16的表达分别为57.1%和71.4%,CyclinD1与CDK4呈正相关关系(P《0.05).CyelinD1与p16呈负相关关系(P《0.05).结论 CyclinD1、CDK4的过度表达与肿瘤的分化程度、淋巴结转移密切相关;CyclinD1的过度表达和p16的低表达在大肠癌发生中起协同作用;大肠癌的发生机制涉及CyclinD1、CDK4和p16调节环路中多个基因的异常.     

细胞周期蛋白D1在浸润性乳腺癌中的表达及其临床意义

目的　探讨浸润性乳腺癌组织中细胞周期蛋白D 1(cyclinD1)的表达 ,及其与激素受体和临床病理特征的相关性。方法　采用免疫组化方法检测 97例浸润性乳腺癌组织和 2 0例正常乳腺组织中cyclinD1的表达情况 ;采用免疫组化方法检测肿瘤组织中的雌、孕激素受体 (ER、PR)的表达。结果　浸润性乳腺癌组织中 ,cyclinD1蛋白表达率 (5 7.7% )显著高于正常乳腺组织(15 .0 % ) (P <0 .0 1)。ER阳性、PR阳性的乳腺癌组织中cyclinD 1表达较ER阴性、PR阴性者增高。cyclinD 1高表达与腋淋巴结转移、肿瘤大小、TNM分期显著相关 ,而与患者年龄、肿瘤病理类型无关。结论　cyclinD1的高表达在乳腺癌的发生、发展中可能起重要作用 ,并与激素受体、腋淋巴结转移、TNM分期相关     

P16蛋白与细胞周期蛋白D1在子宫内膜癌中的表达及临床意义

目的：研究Ｐ１６和细胞周期蛋白Ｄ１在子宫内膜癌中的表达及其临床意义。方法：采用免疫组化ＬＳＡＢ法检测４２例子宫内膜癌中Ｐ１６、细胞周期素Ｄ１的表达。结果：４２例子宫内膜癌中２０例ｐ１６表达阳性，占４７．６％，ｐ１６与子宫内膜癌的细胞分级、临床分期、肌层浸润深度有关（Ｐ〈０．０５）；１７例子宫内膜癌细胞周期素Ｄ１表达阳性，占４０．４％细胞周期素Ｄ１与子宫内膜癌的细胞分级、临床分期、淋巴结转移有关（Ｐ〈０．０５）；ｐ１６、细胞周期素Ｄ１协同表达１５例，均为晚期或低分化癌。结论：ｐ１６、细胞周期素Ｄ１作为细胞周期调节因子参与子宫内膜癌的发生、发展，其协同作用促进子宫内膜癌的发展、且预后不良。     

cyclinD1、CDK4和Rb在大肠癌中的表达及其意义

目的探讨细胞周期调控因子在大肠癌中的表达及其与大肠癌临床病理特征的关系。方法应用免疫组化SP法对70例大肠癌组织及距癌灶3cm以外的癌旁组织、10cm以外的正常组织中cy-clinD1、CDK4和Rb进行检测。结果cyclinD1和CDK4在大肠癌中过度表达,分别为36/70(51.4%)和28/70(40.0%),并与肿瘤的分化程度呈反比,有淋巴结转移的大肠癌,其cyclinD1和CDK4的阳性率分别为70.0%和60.0%,无淋巴结转移的大肠癌阳性率分别为44.0%和32.0%,两者相比差异有显著性(P<0.05)。Rb在大肠癌、癌旁及正常组织中的表达分别为65.7%、78.6%和85.7%。正常组织与癌组织中Rb的阳性率差异有显著性(P<0.01)。cyclinD1与CDK4呈正相关关系(P<0.05)。结论cy-clinD1、CDK4的过度表达与肿瘤的分化程度、淋巴结转移密切相关;大肠癌的发生机制涉及cyclinD1、CDK4和Rb调节环路中多个基因的异常。     

细胞周期调控相关蛋白Cyclin D1、CDK 4和pRb在新疆维吾尔族妇女宫颈癌中的表达及意义

 目的 探讨细胞周期调控相关蛋白Cyclin D1、CDK 4和pRb磷酸化状态在新疆维吾尔族妇女宫颈癌（简称维族）中表达及其意义。方法 应用免疫组织化学方法检测64例维族宫颈癌及43例维族正常宫颈组织中Cyclin D1、CDK 4表达和pRb磷酸化状态。结果 Cyclin D1和CDK4在宫颈癌组中阳性率分别为70%、87%,与正常宫颈组相比,差异有统计学意义（P<0.05）,pRb磷酸化在两组中差异有统计学意义（P<0.01）。结论 Cyclin D1 与CDK4 蛋白的高表达及pRb高磷酸化可能与维族宫颈癌发生发展有关。     

细胞周期相关蛋白在大肠癌中的表达及其意义

目的 探讨细胞周期相关蛋白在大肠癌中的表达及其与大肠癌临床病理特征的关系.方法 应用免疫组化S-P法对70例大肠癌组织及距癌灶3 cm以外的癌旁组织、10 cm以外的正常组织中CyclinDl、CDK4、p16和Pb进行检测.结果 CyclinD1和CDK4在大肠癌中过度表达,分别为36/70(51.4%)和28/70(40.0%),并与肿瘤的分化程度呈反比,有淋巴结转移的大肠癌,其CyclinD1和CDK4的阳性率分别为70.0%和60.0%,无淋巴结转移的大肠癌阳性率分别为44.0%和32.0%,两者相比差异有显著性(P＜0.05),p16在大肠癌中为低表达33/70(47.1%),癌旁组织和正常组织中p16的表达分别为57.1%和71.4%,Rb在大肠癌、癌旁及正常组织中的表达分别为65.7%、78.6%和85.7%.CyclinD1与CDK4呈正相关关系(P＜0.05).CyclinD1与p16、p16与Rb是负相关关系(P＜0.05、P＜0.05).结论 CyclinD1、CDK4的过度表达与肿瘤的分化程度、淋巴结转移密切相关;p16的表达可能受Rb蛋白的负调控;CyclinD1的过度表达和p16的低表达在大肠癌发生中起协同作用;     

p16,Rb,CDK4和cyclinD1在非小细胞肺癌中的表达及其作用

探讨细胞周期调控因子在非小细胞肺癌组织中的表达及作用。方法应用ＬＳＡＢ免疫组化的方法对１２３例原发性非小细胞肺癌进行检测。结果５１．２％的肺癌出现ｃｙｃｌｉｎＤ１的过表达，７７．２％的肿瘤组织表达，ＣＤＫ４，并与肿瘤的分化程度呈反比。有淋巴结转移的肺癌其ｃｙｃｌｉｎＤ１的ＣＤＫ４的阳性率分别为８７．３％和６８．４％。无淋巴结转移的肺癌阳性率分别为１２．６％和３１．５％。两者相比差异有显著性（Ｐ〉／     

细胞周期蛋白D1在人肝细胞癌中的表达及其意义

探讨人原发性肝细胞细胞周期蛋白Ｄ１的表达及其意义。方法采用免疫组化ＡＢＣ法检测了ｃｙｃｌｉｎＤ１在２９例肝癌组织的表达情况,并分析了其表达水平与肝癌病理分级的关系。结果５８．６％（１７／２９）的肝癌组织癌细胞表达ｃｙｃｌｉｎＤ１,而癌旁非肿瘤性肝细胞的阳性率为１８．２％。ｃｙｃｌｉｎＤ１在肝癌中表达的阳性率随着肝癌细胞分化程度的下降呈升高趋势,并且在Ⅱ级和癌旁肝组织之间Ⅰ级和Ⅲ级之间分别具有显著性     

细胞周期蛋白CyelinD1和CDK4在新疆维吾尔族妇女宫颈癌中的表达及意义

目的：探讨CyclinD1和CDK4在新疆维吾尔族妇女宫颈癌发生、发展中的作用及相互关系。方法：采用免疫组化方法，检测100例宫颈癌组织和50例正常宫颈组织中CyclinD1和CDK4蛋白的表达情况。结果：宫颈癌组织中CyclinD1蛋白阳性表达率为75％，高于正常对照组的30％（P〈0．01）；CDK4蛋白阳性表达率（87％），高于正常对照组（44％）（P〈0．01）。结论：CyelinD1和CDK4在新疆维吾尔族妇女宫颈癌中高表达，且与新疆维吾尔族妇女宫颈癌的发生、发展有关。     

Cyclin D1 and prognosis in human breast cancer

We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RB1 and that it is this abnormality that has the more significant impact on survival from breast cancer. © 1996 Wiley-Liss, Inc.     

Cyclin D1 protein expression and function in human breast cancer

Cyclin D1 is a cell-cycle regulator essential for G₁, phase progression and a candidate proto-oncogene implicated in pathogenesis of several human tumour types, including breast carcinomas. In spite of the accumulating genetic evidence, however, there are no data regarding abundance and properties of the cyclin D1 protein in breast cancer. We now report aberrant nuclear overexpression/accumulation of the cyclin D1 protein in about half of the 170 primary breast carcinoma specimens analyzed by monoclonal antibody immunohistochemistry, indicating that the frequency of cyclin D1 abnormalities may be considerably higher than previously deduced from DNA amplification studies. A comparison of the expression patterns in matched lesions at different stages of tumour progression revealed that the cyclin D1 protein aberration appears to reflect a relatively early event and that, when acquired by a tumour, it is maintained throughout breast cancer progression including metastatic spread. In both tumour tissues and breast cancer cell lines, the abundance of this protein shows characteristic variations consistent with a cell-cycle oscillation and the peak levels expressed in G₁. In all 7 cell lines whose retinoblastoma (Rb) protein is mutant or complexed to SV40 T antigen, exceptionally low levels of cyclin D1 protein and mRNA were found. Antibody-mediated and anti-sense oligonucleotide knockout experiments demonstrate the requirement for the cell-cycle regulatory function of cyclin D1 in breast cancer lines with single or multiple copies of the gene and reveal the absence of such a requirement in the cell lines with Rb defects. Our data are consistent with the notion that the emerging “Rb-cyclin D1 pathway” represents a frequent target of oncogenic abnormalities in breast cancer. © 1994 Wiley-Liss, Inc.     

Cyclin D1 in breast cancer pathogenesis.

Taking a perspective on available evidence that emphasizes relevance to human disease, cyclin D1 is solidly established as an oncogene with an important pathogenetic role in breast cancer and other human tumors. However, the precise cellular mechanisms through which aberrant cyclin D1 expression drives human neoplasia are less well established. Indeed, emerging evidence suggests that cyclin D1 might act, predominantly or at least in part, through pathways that do not involve its widely accepted function as a cell cycle regulator. Although therapeutic exploitation of the role of cyclin D1 as a molecular driver of breast cancer carries great promise, it is also suggested that direct targeting of the cyclin D1 gene or gene products may prove more successful than approaches that rely on arguably incomplete knowledge of the oncogenic mechanisms of cyclin D1.     

颌骨骨肉瘤中cyclinD1和CDK4的表达及其意义

分析细胞周期素Ｄ１（ｃｙｃｌｉｎＤ１）和细胞周期素依赖激酶４（ＣＤＫ４）在颌骨骨肉瘤中的表达及意义。方法采用免疫组化ＡＢＣ法检测ｃｙｃｌｉｎＤ１和ＣＤＫ４在２０例颌骨骨肉瘤和８例骨软骨瘤中的表达。结果骨肉瘤中ｃｙｃｌｉｎＤ１和ＣＤＫ４的阳性率表达率分别为６５．００％（１３／２０）和６０．００％（１２／２０），两者的阳性表达存在正相关（γＳ＝０．４８，Ｐ〈０．０５）；而它们在骨软骨瘤中的阳性率均为１     

Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment.

BACKGROUND: Elevated levels of the cell cycle protein cyclin E, and low levels of its inhibitor, p27(Kip1), have been associated with a poor prognosis following breast cancer. Some studies have found that germline mutations in the breast cancer susceptibility gene, BRCA1, are also associated with an inferior survival rate. The relationship between cyclin E/p27(Kip1) levels, BRCA1 status and outcome has not been studied in detail. PATIENTS AND METHODS: We analyzed a historical cohort of 288 Ashkenazi Jewish women who were diagnosed with breast cancer between 1980 and 1995 and were previously tested for BRCA1/2 mutations. Protein levels of cyclin E and p27(Kip1) were assessed by immunohistochemistry. Breast cancer-specific survival (BCSS) was the main outcome measured. RESULTS: The median follow-up was 8 years. Thirty tumors carried germline BRCA1 mutations. These tumors were more likely to have high cyclin E protein levels [odds ratio (OR) 9.5; P <0.001] and low p27(Kip1) protein levels (OR 2.8; P=0.03) than tumors from patients without BRCA1/2 mutations. High cyclin E expression level was the strongest predictor of BRCA1 germline mutations (multivariate OR 4.7; P=0.004). On univariate analysis, high cyclin E protein levels [relative risk (RR) 2.6; P <0.001] and low p27(Kip1) protein levels (RR 2.3; P=0.006) were significant prognostic factors for a poorer BCSS. In Cox multivariate models, high cyclin E levels remained an independent indicator of poor outcome only in the subgroup of patients who did not receive chemotherapy (P=0.002). CONCLUSIONS: In this ethnically restricted cohort, a high level of cyclin E is a characteristic of BRCA1-related breast cancer, and is a marker of poor prognosis following breast cancer, particularly in the absence of adjuvant chemotherapy.     

散发性乳腺癌中DJ-1蛋白高表达与不良预后

目的 探讨DJ-1蛋白表达水平在散发性乳腺癌发生、发展及预后中的临床意义.方法 采用免疫组织化学法检测了包含199例散发性乳腺癌组织与160例乳腺良性增生组织的组织微阵列芯片中DJ-1蛋白的表达情况,同时应用酶联免疫吸附试验检测48例散发性乳腺癌及35例乳腺良性增生患者血清中DJ-1蛋白的水平,并分析组织中DJ-1蛋白表达水平与乳腺癌患者临床病理指标及生存资料的相关性.统计分析采用Pearson ×^2检验和独立样本t检验;生存分析采用log-rank检验绘制Kaplan-Meier曲线,Cox回归用于进行多变量分析.结果 DJ-1蛋白在乳腺良性增生组织及乳腺癌组织中阳性表达率分别为33.8％ （54/160）、48.7％（97/199）,在乳腺良性增生及乳腺癌患者血清中DJ-1蛋白平均水平分别为（25.86±7.28） ng/ml和（31.31±8.39） ng/ml,与乳腺良性增生相比,乳腺癌组织（×^2=8.182,P=0.004）及血清（t=3.161,P=0.002）中DJ-1蛋白的表达水平均显著增加;淋巴结转移阳性的乳腺癌组织与阴性组织相比,DJ-1表达水平显著增加（×^2=5.372,P=0.020）;随着组织学分级的增加,浸润性导管癌中DJ-1表达水平显著增高（×^2=5.244,P=0.022）;DJ-1阳性表达与患者生存期缩短显著相关（OS：×^2=5.427,P=0.020;×^2=4.606,DFS：P=0.032）.单变量Cox回归分析发现,DJ-1表达水平作为危险因素与患者的OS及DFS显著相关（OS：P=0.023; DFS：P=0.036）,但多变量Cox回归分析发现,DJ-1表达水平并非影响患者预后的独立风险因素（OS：P=0.561; DFS：P=0.342）.结论 在散发性乳腺癌中,DJ-1蛋白表达水平显著增高,其高表达与乳腺癌的侵袭转移、病程进展及不良预后相关.     

Cyclin D1 expression in breast cancer patients receiving adjuvant tamoxifen-based therapy.

PURPOSE: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor-positive breast cancer patients who were treated with tamoxifen-based therapy. EXPERIMENTAL DESIGN: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors. RESULTS: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1-positive tumors compared with patients with cyclin D1-negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1-positive tumors than in patients with cyclin D1-negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]. CONCLUSION: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen-based therapy.