前列腺癌与前列腺增生Ki-67/PCNA mRNA特异性表达比值的研究

目的 以实时荧光定量RT-PCR技术研究良性前列腺增生(BPH)与前列腺癌(PCa)组织标本Ki-67蛋白和组织核增殖抗原(PCNA)mRNA的比值,探讨此比值在PCa诊断中的特异性意义.方法 通过实时荧光定量RT-PCR检测63例PCa和37例BPH前列腺组织Ki-67/PCNAmRNA的表达,比较其在PCa与BPH组织中定量的差异.结果 BPH与PCa组织Ki-67/PCNA mRNA的定量表达值分别为2.264±0.460与5.905±0.780,差异有统计学意义(P＜0.05).结论 实时荧光定量RT-PCR检测Ki-67/PCNA mRNA为PCa的诊断提供了可靠的辅助指标.     

动脉化疗栓塞对膀胱癌组织中Ki-67和PCNA表达的影响

目的：探讨术前动脉化疗栓塞对膀胱癌组织Ki-67和增殖细胞核抗原（PCNA）表达的影响及其临床意义。方法：对30例膀胱癌患者化疗栓塞前后的肿瘤组织,应用免疫组织化学法测定Ki-67和PCNA的表达,并分析Ki-67和PCNA与膀胱癌病理分级和临床分期的关系。结果：对30例膀胱癌患者化疗栓塞前后的肿瘤组织,应用免疫组织化学法测定Ki-67和PCNA的表达,并分析Ki-67和PCNA与膀胱癌病理分级和临床分期的关系。结论：化疗栓塞前后Ki67中高度阳性表达率为70％、26.67％,PCNA为73.33％、20％,差异均有非常显著性意义（P〈0.01）,经随访24.6个月,复发率为16.67％。Ki-67和PCNA阳性表达及下降幅度与膀朊癌的病理分级、临床分期和患者术后复发率关系密切,两者阳性表达及表达强度呈正相关（P〈0.001）。结论：术前化疗栓塞能降低膀胱癌组织Ki-67和PCNA的表达,调节膀胱癌的分化程度,使肿瘤降级降期,减少术后转移,降低复发率,提高生存率。Ki-67和PCNA的表达可作为膀胱癌预后估计的指标。     

自然流产小鼠蜕膜组织中PCNA、Ki-67和survivin表达水平的研究

目的比较正常妊娠和自然流产小鼠模型蜕膜组织中增殖细胞核抗原（PCNA）、细胞增殖标记物Ki-67和凋亡蛋白抑制因子suvivin的表达情况,探讨自然流产的发病机制。方法建立正常妊娠模型CBAXBALB／c和自然流产模型CBAXDBA／2。采用免疫组化SP法测定两组模型孕13d蜕膜细胞PCNA、Ki-67和suvivin的表达。结果与正常妊娠模型相比,自然流产模型蜕膜细胞PCNA的表达显著降低（P〈0．05）;Ki-67和survivin表达降低非常显著（P〈0．01）。结论自然流产小鼠蜕膜细胞PCNA、Ki-67和survivin表达水平低下可能与自然流产的发生有关。     

Proliferating-cell nuclear antigen (PCNA) as an independent prognostic marker in patients after prostatectomy: a comparison of PCNA and Ki-67

OBJECTIVE: To investigate the prognostic value of prostatic tumour cell proliferation, as measured by Ki-67 and proliferating cell nuclear antigen (PCNA), and to compare these measures in men at low and high risk for progression of tumour. PATIENTS AND METHODS: Two groups of patients with prostate cancer, i.e. 'metastatic' (M, 22) who had pT3b-4aN0M0 and pTanyN1M0, and 'nonmetastatic' (NM, 18), who had < or =pT3aN0M0 disease, were selected from a well-examined and mapped group of 114 treated by radical prostatectomy. Patients in the NM group were selected by the criteria of having a Gleason score of < or = 7. To assess proliferation, 1000 cells were counted at x 400 magnification by two observers and the percentage of tumour cells positively stained with Ki-67 and PCNA defined as the Ki-67 and PCNA labelling index (LI), respectively. The two LI were compared in the NM and M groups, and the correlation of the LIs with pathological stage, progression and prostate-specific antigen (PSA)-free survival evaluated. Prognostic values of the LI were analysed using multivariate analysis. RESULTS: The mean (range) follow-up was 33 (4-78) months. The mean LIs were higher in the M than the NM group for both PCNA and Ki-67 (P = 0.02 and 0.019, respectively). Both LIs were markedly different between the groups when stratified by progression, with both significantly higher in men with progression in the NM group. Both LIs had a significant association with Gleason score, pathological stage, progression and PSA-free survival. In multivariate analysis the PCNA LI, surgical margin status and pathological stage were independent factors for progression. CONCLUSION: Tumour cell proliferation as assessed by Ki-67 or PCNA correlate significantly with progression. The PCNA LI was an independent predictor of progression, especially in patients with a low risk of progression according to predefined criteria.     

Prognostic role of Ki-67 score in localized prostate cancer: A systematic review and meta-analysis

Background

Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically.

膀胱癌CK20及Ki-67的表达及相关性

目的 探讨角蛋白20(CK20)和Ki-67在膀胱癌中的表达与膀胱癌的侵袭、转移及预后的关系.方法 用免疫组织化学SP法检测154例膀胱癌组织中CK20和Ki-67的表达.结果 CK20在103例肿瘤组织中有表达,阳性率为66.9%.CK20的表达和膀胱癌的T分期及远处转移呈正相关(P<0.05).Ki-67在126例肿瘤组织中有阳性表达,阳性率为81.8%.Ki-67在膀胱癌组织的表达与肿瘤病理分级、T分期、远处转移呈正相关(P<0.05).Spearman等级相关分析表明两者明显相关(P<0.05).结论 CK20及Ki-67可能参与了膀胱癌的侵袭与转移,CK20与Ki-67可作为预后判断因子,结合病理分级和临床分期分析能提高对膀胱癌患者预后判断的准确性.     

膀胱癌CK20及Ki-67的表达及相关性

目的 探讨角蛋白20(CK20)和Ki-67在膀胱癌中的表达与膀胱癌的侵袭、转移及预后的关系.方法 用免疫组织化学SP法检测154例膀胱癌组织中CK20和Ki-67的表达.结果 CK20在103例肿瘤组织中有表达,阳性率为66.9%.CK20的表达和膀胱癌的T分期及远处转移呈正相关(P<0.05).Ki-67在126例肿瘤组织中有阳性表达,阳性率为81.8%.Ki-67在膀胱癌组织的表达与肿瘤病理分级、T分期、远处转移呈正相关(P<0.05).Spearman等级相关分析表明两者明显相关(P<0.05).结论 CK20及Ki-67可能参与了膀胱癌的侵袭与转移,CK20与Ki-67可作为预后判断因子,结合病理分级和临床分期分析能提高对膀胱癌患者预后判断的准确性.     

The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas

Summary In order to improve our ability to predict the regrowth of nonfunctioning pituitary adenomas, we tried to assess the correlation between growth fractions with Ki-67 and PCNA (proliferating cell nuclear antigen) and tumour doubling times in regrowing tumours, and also to find out any difference of growth fractions between the regrowing and the cured cases.In 33 patients with non-functioning pituitary adenomas, 14 cases including 11 with cavernous sinus invasion showed residual tumour on MRI after the operation (regrowing group) and 19 cases had no tumour regrowth on MRI within 5 years after the operation (cured group). Immunocytochemical studies were done with monoclonal antibodies (anti-PCNA, anti-Ki-67: MIB-1). The growth fraction of each tumour was estimated by calculating the ratio of the positive nuclei to the total number of tumour cells with the aid of an image analyser (Mac SCOPE). The tumour doubling times were estimated from serial CT or MRI with the aid of the image analyser (NIH image).Ki-67 staining indices ranged from 0.2% to 1.5% (n = 14, 0.86±0.10%; mean±SEM) in the regrowing group, and from 0.1% to 0.5% (n = 19, 0.23±0.03%) in the cured group. PCNA staining indices of the regrowing group ranged from 0.6% to 24% (n = 14, 3.7±1.6%). In the regrowing group, the tumour doubling times ranged from 200 to 2550 days (930±180 days), and showed a significant inverse correlation with Ki-67 staining indices, but no correlation with PCNA staining indices. The regrowing group showed a significantly higher Ki-67 staining index (n = 14, 0.86±0.10%) than the cured group (n = 19, 0.23±0.03%) (p<0.01).These results indicate that immunocytochemical studies using MIB-1 may be better than those with PCNA for the prediction of regrowth in non-functioning pituitary adenomas. Immunocytochemical study with MIB-1 could lead to the accurate prediction of the rapid regrowing lesions in non-functioning adenomas.     

Hvin和Ki-67蛋白在胆管癌组织中表达的意义

目的 探讨Livin和Ki-67蛋白在胆管癌组织中的表达及两者之间的关系和临床意义.方法 采用SP法检测2002年1月至2003年12月中国医科大学附属盛京医院手术切除的55例胆管癌组织和12例慢性胆管炎组织中Livin和Ki-67蛋白的表达,并分析这两种蛋白与胆管癌临床病理特征的关系.应用Spearman等级相关分析、χ2检验和t检验对结果进行分析.结果 Livin蛋白在胆管癌标本中的阳性表达率为71%(39/55),明显高于慢性胆管炎标本的0(0/12)(χ2=20.361,P<0.01);Livin蛋白的表达受胆管癌患者的分化程度和淋巴结转移影响(χ2=4.193,4.245,P<0.05).Ki-67蛋白在胆管癌标本中的阳性表达率为96%(53/55).临床Ⅰ、Ⅱ、Ⅲ、Ⅳ期患者Ki-67标记指数分别为22%±16%、33%±12%、43%±15%、49%±10%,Ⅱ、Ⅲ、Ⅳ期与Ⅰ期比较差异有统计学意义(t=2.307,2.871,3.957,P<0.05);有无局部淋巴结转移的患者Ki-67标记指数分别为43%±13%、34%±16%,两者比较差异有统计学意义(t=2.334,P<0.05).胆管癌组织中Livin蛋白的表达与Ki-67标记指数呈正相关(r=0.502,P<0.01).结论 Livin蛋白在胆管癌的发生、发展中起重要作用,并且与胆管癌增殖活性相关,两者结合可作为胆管癌恶性程度和判断预后的标准.     

Runx3和Ki-67蛋白在皮肤恶性黑色素瘤中的表达

目的：检测Runx3和Ki-67蛋白在皮肤恶性黑色素瘤（CMM）中的表达水平,以探讨Runx3和Ki-67在CMM发生、发展过程中的作用。方法：采用免疫组织化学法研究Runx3和Ki-67蛋白在皮肤恶性黑色素瘤、皮肤交界痣及正常皮肤中的表达。结果：Runx3蛋白在CMM中阳性表达率为23.68%,与皮肤交界痣（85.00%）和正常皮肤（90.00%）相比,差异具有统计学意义（P〈0.05）;Ki-67蛋白在CMM中阳性表达率为78.95%,与皮肤交界痣（25.00%）和正常皮肤（25.00%）相比差异具有统计学意义（P〈0.05）。结论：皮肤恶性黑色素瘤的产生可能与Runx3蛋白的表达降低及Ki-67蛋白的表达升高有关。     

膀胱癌CK20及Ki-67的表达及相关性

目的 探讨角蛋白20(CK20)和Ki-67在膀胱癌中的表达与膀胱癌的侵袭、转移及预后的关系.方法 用免疫组织化学SP法检测154例膀胱癌组织中CK20和Ki-67的表达.结果 CK20在103例肿瘤组织中有表达,阳性率为66.9%.CK20的表达和膀胱癌的T分期及远处转移呈正相关(P<0.05).Ki-67在126例肿瘤组织中有阳性表达,阳性率为81.8%.Ki-67在膀胱癌组织的表达与肿瘤病理分级、T分期、远处转移呈正相关(P<0.05).Spearman等级相关分析表明两者明显相关(P<0.05).结论 CK20及Ki-67可能参与了膀胱癌的侵袭与转移,CK20与Ki-67可作为预后判断因子,结合病理分级和临床分期分析能提高对膀胱癌患者预后判断的准确性.     

p53 and Ki-67 expression as prognostic factors in cystosarcoma phyllodes

We have reviewed the histopathological, clinical outcome and immunohistochemical status in 21 women with cystosarcoma phyllodes (CSP) tumors of the breast. We assessed 12 tumors as histopathologically benign and 9 tumors as malignant. The median patient ages in benign and malignant CSP tumors were 39.6 and 45.4 years of age, respectively. The stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour, and heterologous stromal elements were significant features of the malignant CSP tumors. Benign CSP tumors were predominantly of fibroadenomatous architecture with cellular stroma (mild or moderate) and some distortion and elongation of glandular elements. Five malignant CSP tumors were stained positively with p53, and 6 malignant CSP tumors were stained immunohistochemically with Ki-67. All benign CSP tumors were negatively stained for p53 and Ki-67. The patients with benign CSP tumors were treated with local excision ( n = 11) and with subcutaneous mastectomy ( n = 1). Malignant CSP tumors were treated with wide local excision ( n = 1), partial mastectomy ( n = 1), simple mastectomy ( n = 2), and modified radical mastectomy ( n = 5). Two patients with a high mitotic rate and high values of p53 and Ki-67 received additional radiotherapy and chemotherapy. One case had liver metastasis. This tumor had high mitotic figures, stromal overgrowth, severe stromal cellularity, and 20% Ki-67 and mild p53 positivity. We suggest that p53 and Ki-67 can play an important role in predicting prognosis and yielding additional therapy besides conventional prognostic factors in the treatment of the CSP patients.     

Prognostic value of cell proliferation (Ki-67 antigen) and nuclear DNA content in clinically resectable, distal bile duct carcinoma

Background: The aim of this study was to investigate the prognostic value of cell proliferation (Ki-67 antigen) and DNA content in patients resected for distal bile duct carcinoma (DBDC). Methods: Formalin-fixed tumor specimens of 35 patients with resected DBDC and a long-term clinical follow-up were analyzed. MIB-1 antibody was used for Ki-67 antigen detection to determine the proportion of proliferating cells. DNA content was measured using flow cytometry. Results: A significant correlation was found between a low MIB-1 index (<20%) and survival (P<.05). Of the 35 tumor specimens, 34 specimens were evaluable by flow cytometry: 22 carcinomas were diploid (65%), and 12 were aneuploid (35%). The median DNA index of aneuploid tumors was 1.36 (range, 1.09 to 1.76). No correlation of DNA-ploidy with survival time was found. Conclusion: In contrast to DNA-ploidy pattern, Ki-67 antigen expression showed prognostic significance in resectable DBDC. A Ki-67 positive ratio of 20% was associated with decreased survival time.     

Rac1及Ki-67因子在人翼状胬肉中的表达

目的：研究Rac1蛋白和Ki-67在人翼状胬肉中的表达,分析二者在翼状胬肉表达的相关性,探讨利用Rac1作为标记物评估翼状胬肉生物学特性,为临床诊疗提供参考。方法：应用辣根过氧化物酶标记的链霉卵白素免疫组织化学方法（S-P法）对39例原发性翼状胬肉及12例正常球结膜组织中的Rac1及Ki-67蛋白进行检测。结果：Rac1及Ki-67蛋白在翼状胬肉组织中的表达均高于正常结膜组,差异有显著性意义（Z=-3.386,Z=2.707,P均〈0.05）。Rac1及Ki-67蛋白表达之间的相关系数r=0.384,差异无显著性意义（P〉0.05）。结论：Rac1及Ki-67在翼状胬肉中的高度表达,提示翼状胬肉在细胞骨架,基底膜分解代谢和细胞增殖活跃方面发生了变化。     

乳腺浸润性导管癌组织中COX-2和Ki-67的表达及相关性分析

目的探讨环氧化酶-2（COX-2）和Ki-67在乳腺浸润性导管癌组织中的表达情况及其临床意义。方法采用免疫组织化学sP方法检测82例乳腺浸润性导管癌组织和相应癌旁正常组织中COX．2和Ki．67蛋白表达,并分析二者表达的相关性以及其表达与乳腺浸润性导管癌患者临床病理特征的关系。结果①在82例乳腺浸润性导管癌组织中COX-2和Ki．67蛋白表达阳性率均分别明显高于其在相应癌旁正常组织中的表达阳性率[COX．2：71．95％（59／82）比8．54％（7／82）,z。=68．56,P〈0．001;Ki-67：64．63％（53／82）比13．42％（11／82）。X2=45．20,P〈0．001]。②COX．2和Ki．67蛋白阳性表达与肿瘤TNM分期（cox．2：rs=O．349,P〈0．05;Ki．67：rs=0．305,P〈0．05）、淋巴结转移（cOx-2：rs=0．336,P〈0．05;Ki-67：rs=0．419,P〈0．01）、脉管侵犯（cOx-2：rs=0．235,P〈0．05 ki-67：rs=0．461,P〈0．01）及组织学分级（cox-2：rs=0．434,P〈0．01;Ki-67：rs=0．378,P〈0．05）均呈正相关;Ki．67蛋白阳性表达与肿瘤直径呈正相关（rs=0．365,P〈0．01）,而COX．2蛋白阳性表达与此无关（rs=0．135,P〉0．05）;COX-2和Ki-67蛋白阳性表达皆与患者是否绝经无关（cox-2：rs=O．172,P〉0．05;Ki．67：rs=0．163,P〉0．05）。③在浸润性导管癌组织中COX．2和幻．67蛋白阳性表达呈正相关性（rs=0．475,P〈0．01）。结论在乳腺浸润性导管癌组织中COX．2和Ki．67的表达均增高,两者与乳腺浸润性导管癌临床病理特征密切相关,对两者进行联合检测可反映乳腺浸润性导管癌的生物学行为,COX-2有可能成为乳腺癌治疗的一个新靶点。     

Ki-67启动子转录调控结构与功能研究

目的 观察Ki-67核心启动子调控元件对转录调控的影响.方法 根据Ki-67启动子结构软件分析结果,对Ki-67核心启动子(-223～+30)内的5个调控区域,包括(+13～+30)及4个潜在Sp1结合位点(-198～-172)、(-170～-144)、(-63～-37)和(-14～+12)进行内部缺失,目的片段缺失的Ki-67核心启动子插入pGL3-Basic载体,构建报告基因重组体质粒.将重组体分别转染肿瘤Hela、SW1990、SGC-7901、A549细胞株,使用双荧光素酶报告基因检测系统测定其转录活性,并与Ki-67核心启动子质粒pGLBK2+转录活性比较.结果 缺失(+13～+30)的启动子重组体质粒在4种肿瘤细胞的转录功能均有显著提高,分别达到缺失前的1.2、2.0、1.7、1.4倍.缺失潜在Sp1结合位点的4个启动子重组体在4种肿瘤细胞的转录功能均有显著降低,其中缺失(-170～-144)后转录活性最小,在4种肿瘤细胞中分别降至未缺失前的16.2%、10.4%、6.7%、12.2%.结论 Ki-67启动子(+13～+30)区包含负性调控元件,对其缺失后形成的新的Ki-67核心启动子(-223～+12)是更好的调控肿瘤基因治疗的启动子.(-198～-172)、(-170～-144)、(-63～-37)和(-14～+12)可能存在潜在的Sp1顺式作用元件,其中-170～-144区域的顺式作用元件最为重要.     

膀胱癌组织中Ki-67、p63的表达与肿瘤复发的关系

目的:探讨浅表性膀胱癌组织学形态以及Ki67、p63表达与肿瘤复发的关系。方法:将3年来随访的60例浅表性膀胱癌分为复发组和无复发组。免疫组化法检测Ki-67和p63的表达并比较复发组与无复发组的差异。结果:在平均28个月的随访中,40例复发,复发1~4次,Ki-67和p63阳性率在两组之间有明显差别,复发组均明显高于无复发组(P<0.05)。在不同病理分级TCC中p63和Ki-67表达有明显差异,病理分级高的明显高于分级低的(P<0.01)。结论:Ki-67、p63阳性表达尤其是联合阳性表达对判断膀胱癌复发具有重要意义。     

Ki-67核心启动子在胃癌SCG-991细胞中的转录活性

目的 观察Ki-67核心启动子在人胃癌细胞中的转录活性.方法 使用缺失分析法分别从5'端和3'端对Ki-67基因启动子逐段缺失,得到不同长度的8个和3个截短DNA片段.分别插入pGL3-Basic载体后转染人胃癌SCG-991细胞,使用双荧光素酶检测系统鉴定转录活性,确定Ki-67基因核心启动子.比较Ki-67核心启动子与另2种肿瘤启动子hTERT和Survivin的转录活性.结果 自5'端缺失得到的-223～+771截短片段在SCG-991细胞内转录活性达到病毒SV40启动子活性的56.5%;自3'端缺失的-223～+30截短片段转录活性更强,为-223～+771片段活性的2.1倍,是hTERT启动子的1.7及Survivin启动子和15.3倍.结论 Ki-67核心启动子区域为-223～+30,在胃癌SCG-991细胞中的转录活性超过SV40启动子,以及hTERT启动子及Survivin启动子.     

膀胱移行细胞癌中Survivin与Ki-67、p53的表达及临床意义

目的 探讨膀胱移行细胞癌中Survivin、p53及Ki-67的表达与膀胱移行细胞癌临床病理特征的关系及其临床意义. 方法 用免疫组织化学方法 检测88例膀胱移行细胞癌与10例正常膀胱黏膜组织中Survivin、p53及Ki-67的表达,并用RT-PCR方法 验证其中30例膀胱移行细胞癌和10例正常膀胱黏膜组织中Survivin的表达. 结果 免疫组织化学方法 显示在膀胱移行细胞癌中Survivin、p53阳性表达率分别为63.6%(56/88)和45.5%(40/88),正常膀胱黏膜组织中均无表达,差异有统计学意义(P<0.01),且Survivin的表达与膀胱癌的临床分期密切相关(P<0.05).膀胱癌组织中Ki-67增殖指数(PI)为20.4士10.7,正常膀胱黏膜组织中为0.RT-PCR方法 显示在30例膀胱移行细胞癌中Survivin阳性表达率为100%,而正常膀胱黏膜组织中均无表达.结论 Survivin与膀胱癌的恶性程度有关,与p53及Ki-67共同参与了膀胱移行细胞癌的发生、发展及进程.     

膀胱移行细胞癌Ki-67的表达及其意义

目的:探讨Ki-67抗原在膀胱移行细胞癌(BTCC)中的定量表达及其与BTCC生物学行为的关系。方法:用流式细胞技术(FCM)对36例BTCC和10例正常膀胱黏膜细胞组织标本进行Ki-67检测。结果:Ki-67在BTCC组织中的阳性表达率为(10.89±7.88)%,在正常膀胱黏膜组织中的阳性表达率仅为(0.27±0.07)%,两者比较差异有统计学意义(P<0.01);临床分期Tis~T1为(4.93±2.95)%,T2~T4为(18.34±5.24)%,病理分级Ⅰ级为(3.17±0.83)%,Ⅱ级为(10.97±2.35)%,Ⅲ级为(21.60±3.70)%,随着分期分级的增加,Ki-67的表达率也逐步增加,差异有统计学意义(P<0.01)。结论:定量检测Ki-67能准确评估BTCC的生物学行为,Ki-67是膀胱癌的重要肿瘤标记物。