cyclin D3与淋巴瘤细胞增殖相关性的初步研究

目的：初步探讨cyclin D3与淋巴瘤细胞增殖活性的相关性。方法：运用荧光免疫细胞化学法结合激光共聚焦显微镜观察，分析淋巴瘤细胞株Raij细胞内cyclin D3与Ki67表达、定位的关系。通过转染pDsRed-cyclin D3和pSuPER-cyclin D3 siRNA质粒，分析改变eyelin D3表达水平对肿瘤细胞增殖能力的影响。结果：在分裂增殖旺盛的Raji细胞中，Ki67与cyclin D3共定位于细胞核内。导入外源性cyclin D3引起相应细胞核Ki67的表达增加，阻断内源性cyclin D3基因表达，导致同一细胞相同部位Ki67表达水平下降。结论：cyclin D3的表达水平与NHL细胞增殖活性密切相关，提示其可能在淋巴瘤的发生、发展过程中发挥重要作用。     

非霍奇金淋巴瘤中McM7、p53和Ki-67的表达

目的 探讨McM7、p53和Ki-67在非霍奇金淋巴瘤（NHL）中表达的意义及相互关系。方法 应用组织芯片和免疫组化S-P法检测McM7、p53和Ki-67在9例反应性增生淋巴结、175例NHL组织中的表达。结果 NHL各组中McM7标记指数（1abelling index,LI）均高于Ki-67 LI;惰性组中McM7 LI和Ki-67 LI低于侵袭性组和高度侵袭性组,差异有显著性（P＜0．05）。NHL中p53表达的阳性率为23．4％,p53在惰性组、侵袭性组及高度侵袭性组之间的表达差异无显著性（P＞0．05）。Ki-67、p53和McM7三者在NHL中的表达呈平行关系（P＜0．01）。结论 McM7是反映细胞增殖的良好指标,作用优于Ki-67,其表达指数与NHL的组织分型、细胞增殖及恶性程度有关。p53基因突变在大多数NHL的发生、发展中可能并不是一个主要的分子事件。     

甲状腺肿瘤中survivin和Ki-67的表达

目的 探讨凋亡抑制蛋白survivin和Ki-67抗原在甲状腺肿瘤组织中的表达及其临床病理意义.方法 选择术后切除的甲状腺癌标本56例、甲状腺腺瘤13例、腺瘤旁正常甲状腺组织10例,采用SP法染色,观察survivin、Ki-67抗原的表达情况,结合临床病理资料进行统计学分析.结果 正常甲状腺组织、甲状腺腺瘤和甲状腺癌患者中survivin阳性表达依次为0、15.38%和60.71%;Ki-67阳性表达依次为0、23.08%和69.64%,甲状腺癌中survivin和Ki-67的表达明显高于正常甲状腺组织和甲状腺腺瘤(P<0.05).年龄>45岁组甲状腺癌survivin表达明显高于<45岁组(P<0.05);而Ki-67表达无年龄差异(P>0.05).survivin和Ki-67表达与甲状腺癌病理类型无关(P>0.05).TNM分期Ⅲ、Ⅳ期患者的survivin和Ki-67阳性表达明显高于Ⅰ、Ⅱ期患者(P<0.05).在有淋巴结转移的甲状腺癌中survivin和Ki-67阳性表达明显高于无淋巴结转移者(P<0.05).结论 survivin的高表达与甲状腺癌的发生、发展和转移有密切关系.survivin和Ki-67的表达情况对甲状腺癌的诊断和预后评估有一定临床意义.二者联合检测对甲状腺癌的早期诊断可能发挥重要作用.     

乳腺癌和非癌组织中Syk、survivin和Ki-67的表达及其相关性

目的 探讨乳腺癌和非癌组织中Syk、survivin和Ki-67的表达及其相互关系.方法 应用免疫组化SP法检测52例乳腺浸润性导管癌和39例非癌组织(包括癌旁乳腺组织17例和乳腺纤维腺瘤组织22例)中Syk、survivin和Ki-67的表达.结果 39例非癌组织中Syk均呈阳性表达,而survivin及Ki-67均呈阴性表达.52例乳腺癌组织中,Syk阳性22例(42.3%),survivin阳性36例(69.2%),Ki-67阳性32例(61.5%).乳腺癌中Syk阳性表达率低于非癌组织(χ2=31.01, P＜0.01);乳腺癌中survivin(χ2=41.82,P＜0.01)和Ki-67(χ2=34.37,P＜0.01)阳性表达率均高于非癌组织.相关分析显示,Syk与survivin的表达呈负相关(r=-0.53,P＜0.01);Syk与Ki-67的表达相关系数呈负值(r=-0.22,P=0.12);survivin与Ki-67的表达呈正相关(r=0.33,P＜0.05).结论 Syk可能有抑制乳腺癌细胞增殖和促进其凋亡的功能,提示Syk可能是一种抑癌基因,可作为乳腺癌新的分子标记物.联合检测Syk、survivin和Ki-67在乳腺癌中的表达,有望成为估价乳腺癌生物学行为的参考指标.     

卵巢浆液性肿瘤中MCM4与Ki-67的表达及意义

目的 探讨微小染色体维持蛋白4(minichromosome maintenance proteins 4,MCM4)、Ki-67在卵巢浆液性肿瘤中的表达及意义.方法 采用免疫组化EliVision两步法检测MCM4、Ki-67蛋白在10例正常卵巢上皮组织(对照组)、19例卵巢良性浆液性嚢腺瘤、16例交界性浆液性肿瘤和43例浆液性腺癌中的表达.结果 MCM4在对照组、卵巢良性浆液性囊腺瘤、交界性浆液性肿瘤、浆液性腺癌的阳性表达率分别为10.00%、21.05%、43.75%、79.07%,Ki-67在对照组、卵巢浆液性乳头状腺瘤、交界性嚢腺瘤、浆液性腺癌的阳性表达率分别为10.00%、15.79%、25.00%、53.49%,其随着卵巢肿瘤病变的升级呈增高的趋势.MCM4在卵巢浆液性腺癌和交界性浆液性肿瘤中的表达与正常对照组相比差异具有统计学意义(P<0.05).Ki-67在卵巢浆液性癌和交界性浆液性肿瘤中的表达与正常对照组相比差异具有统计学意义(P<0.05).MCM4在卵巢浆液性癌中的表达与临床分期、病理分级及转移[淋巴结转移和(或)器官转移]有明显相关(P<0.05).Ki-67蛋白在卵巢浆液性癌中的表达与病理分级及淋巴结转移有明显相关(P<0.05),MCM4和Ki-67呈正相关.结论 MCM4、Ki-67为卵巢浆液性肿瘤的增殖指标,用于卵巢良、恶性肿瘤的鉴别和诊断,并可初步评估肿瘤预后,指导临床治疗.     

PCNA与Ki-67在葡萄胎患者宫内不同部位组织中的表达及临床意义

目的探讨PCNA和Ki-67在葡萄胎患者宫内不同部位组织中的表达对葡萄胎治疗及预后判断的意义.方法采用免疫组化S-P法检测38例葡萄胎患者宫腔中央水泡样胎块及靠宫壁蜕膜样组织中PCNA和Ki-67的表达.结果 1.PCNA及Ki-67在宫中央组织阳性表达均大于靠宫壁组织.P＜0.05,有明显差异.2.完全性葡萄胎PCNA及Ki-67阳性表达>部分性葡萄胎.浸润性葡萄胎PCNA及Ki-67阳性表达>完全性葡萄胎,且均为强阳性表达.3.PCNA和Ki-67在两组织中均有阳性表达,PCNA的表达更为明显,P＜0.05(宫内)P＜0.05(宫壁),有显著差异.结论葡萄胎宫内水泡样组织的增殖活性明显大于靠宫壁的组织,必须彻底刮净宫内组织方能预防恶变的发生.靠宫壁组织因其增殖活性较弱,可不必常规二次刮宫,以避免过度搔刮带来的过度损伤.葡萄胎的细胞增殖程度可能随疾病进展而逐渐增强,对于宫内、宫壁组织均有强阳性表达的患者要警惕其恶变的可能.PCNA与Ki-67能代表葡萄胎滋养细胞异常增生的客观指标,其检测简便、快捷、价廉,有临床价值,值得推广.     

子宫颈非典型不成熟鳞状上皮化生与子宫颈鳞状上皮内瘤变Ⅲ级形态学及增殖分化特征比较

目的 探讨子宫颈非典型性不成熟鳞状上皮化生(AIM)与子宫颈CINⅢ形态学及增殖分化特征的差异.方法 采用形态学观察,AB黏液组化染色,细胞增殖相关抗原Ki-67和角蛋白(CK)10、14免疫组化染色方法 ,观察55例原诊断为CINⅢ的病例和14例子宫颈息肉伴成熟性鳞状上皮化生(OSM)组织病理学特征,黏液残留情况,细胞增殖活性和分化程度;采用半巢式PCR检测HPV16E6DNA.结果 (1)参照Crum的组织学诊断标准,在CIN Ⅲ中有1例经组织形态观察符合AIM的诊断标准,即重新诊断为AIM;(2)根据鳞状上皮中的黏液残留情况,从55例CINⅢ中鉴别出7例AIM;(3)AIM的Ki-67表达高于OSM(P=0.022),明显低于CIN Ⅲ(P=0.000)差异有统计学意义;(4)CK10在AIM和CIN Ⅲ中的表达差异有统计学意义(P=0.000);CK14在AIM和CINⅢ组间的表达差异无统计学意义(P=1.000);(5)AIM的HPV16感染检出率为71.4%与CIN Ⅲ的榆出率85.4%相比差异无统计学意义(P=0.321).结论 在Crum的AIM形态学诊断标准基础上,结合本研究中各项指标的研究结果 ,本研究提出AIM与CIN Ⅲ的鉴别诊断依据:①核分裂象数≤15/10 HPF,位于上皮下1/3层;②病理性核分裂象罕见;③AB染色显示有黏液残留;④Ki-67 PI<50%;⑤CK10弥漫表达于除基底副基底层外黏膜上皮各层.     

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。     

食管鳞状细胞癌中MCM2蛋白与Ki-67的表达及对比研究

目的 探讨微小染色体维持蛋白2(minichromosome maintenance 2 protein,MCM2)与Ki-67在食管癌中的表达及两者表达的差异和相关性.方法 采用免疫组化EliVision方法,分别检测90例食管鳞状细胞癌组织中MCM2,Ki-67的表达,计算其标记指数(labeling index,LI),分析MCM2,Ki-67在食管鳞癌中的表达及两者之间的差异和相关性.结果 90例食管癌组织均表达MCM2及Ki-67抗原,其中MCM2 LI高于Ki-67,两者差异有统计学意义(P＜0.05).同时显示MCM2及Ki-67的表达与食管鳞癌的分化程度具有相关性,MCM2在食管鳞癌各级组织间表达差异均有统计学意义(P＜0.01),而Ki-67只在Ⅰ级与Ⅲ级食管鳞癌组织间差异有统计学意义(P＜0.01).并且MCM2与Ki-67在食管鳞癌中的表达呈正相关关系(P＜0.01).结论 MCM2是优于Ki-67的细胞增殖标记物,可用于对食管鳞癌的分级和判断食管鳞癌恶性程度的高低.     

Midkine expression in colorectal tumors: correlation with Ki-67 labeling in sporadic, but not ulcerative colitis-associated ones

Midkine (MK) is a heparin-binding growth factor encoded by a retinoic acid responsive gene. To investigate the possible contribution of MK to genesis of colorectal carcinomas, an immunohistochemical examination of protein expression was conducted in sporadic and ulcerative colitis (UC)-associated tumors. MK expression significantly differed among normal mucosa, adenomas with low-grade dysplasia (LGD), adenomas with high-grade dysplasia (HGD) and invasive adenocarcinomas: MK expression was increased along with tumor progression. UC-associated lesions (regenerative mucosa of UC, UC-associated dysplasia and UC-associated adenocarcinoma) had similar variations. MK expression in UC-associated lesions was significantly higher than in normal mucosa, although there was no significant difference among UC-associated lesions. However, in UC-associated dysplasia, MK expression did not differ between the upper and lower halves, in contrast to adenoma with LGD and HGD, in which MK expression was significantly higher in the upper than lower halves, corresponding to cell proliferative zone. Furthermore, correlations with Ki-67 and single-strand DNA labeling, respectively, reflecting cellular proliferative activity and apoptosis, were noted in sporadic but not UC-associated lesions. These results suggest that MK is involved in genesis/development of sporadic colorectal tumors as well as of UC-associated tumors, but might contribute differently to genesis/development in these two types of tumors.     

Clinicopathologic relevance of apoptotic and proliferative factors in human lung adenocarcinoma: Fas expression correlates with the histologic subtype,but not with the degree of apoptosis

We immunohistochemically examined 141 surgically resected peripheral lung adenocarcinomas for the expression of Fas, single stranded (ss-) DNA and Ki-67, and statistically evaluated the relationship of these parameters with other clinicopathologic variables, including clinical stage, nodal involvement, and histopathologic subtypes classified according to WHO criteria. Fas expression by cancer cells was characteristically localized in the cytoplasm, and the extent of expression correlated well with the degree of Ki-67 reactivity (p = 0.0004), but not with the degree of apoptic occurrence, as assessed by ss-DNA reactivity. Cancer cells of the bronchioloalveolar carcinoma (BAC) subtype without invasive growth exhibited a significantly lower Fas expression than those of other subtypes (p < 0.0001). Positive expression of Fas was frequently associated with a high incidence of nodal involvement and advanced clinical stage, as compared with cases of negative expression (p = 0.0111 and p = 0.0439, respectively). Multivariate analysis revealed that Fas expression significantly correlated with the histologic subtype, but not with tumor size, nodal involvement, or clinical stage. Survival analysis determined by the log-rank test revealed that clinical stage and Ki-67 reactivity were poor prognostic variables, and Fas expression was not statistically significant. Based on these data, intracytoplasmic expression of Fas in cancer cells may participate in the development of resistance to fas-mediated apoptosis.     

Diagnostic utility and prognostic significance of the Ki-67 labeling index in diffuse large B-cell lymphoma transformed from follicular lymphoma: a study of 76 patients

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki-67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B-cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki-67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression-free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki-67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes.     

Ki-67及ezrin在子宫内膜腺癌中的表达及意义

目的　探讨Ki 6 7及ezrin在子宫内膜癌中的表达及意义。方法　应用免疫组化方法检测Ki 6 7和ezrin在子宫内膜腺癌、非典型增生、子宫内膜增殖症及正常内膜中的表达 ;应用RT PCR技术对Ki 6 7 和ezrin mRNA在子宫内膜癌及正常内膜中的表达进行半定量分析。结果　Ki 6 7指数在子宫内膜癌、非典型增生及子宫内膜增殖症分别为 39.9± 6 .4、1 8.9± 1 4 .7、1 8.6± 1 5 .3,明显高于正常子宫内膜的 1 .1± 1 .6 7(P <0 .0 5 )。正常及子宫内膜增殖症的ezrin表达几乎全集中于细胞膜上 ,而子宫内膜癌及非典型增生的ezrin表达则为细胞浆内的弥漫性染色。在子宫内膜癌组织中 ,Ki 6 7mRNA表达为 0 .6 0 75± 0 .0 887,高于正常内膜组织的 0 .35 32± 0 .1 2 6 7。结论　Ki 6 7抗原过量表达与子宫内膜癌的发生及恶性程度密切相关 ;ezrin的着色部位对子宫内膜病变的性质有标识作用     

The anaplastic variant of centrocytic lymphoma is marked by frequent rearrangements of the bcl-1 gene and high proliferation indices

Ten cases of classic centrocytic lymphoma as defined in the Kiel classification system were investigated for their immunophenotype, their proliferation activity and by means of molecular diagnostics. The findings were compared to those obtained from a group of nine cases of anaplastic centrocytic lymphoma. Both groups showed virtually identical immunohistochemical characteristics with positivity for CD5 and negativity for CD10 and CD23. In the group of anaplastic centrocytic lymphoma, there were considerably higher proliferation indices as documented by staining for the Ki-67 antigen, up to 80% of the tumour cells being positive. Moreover, the cases of anaplastic centrocytic lymphoma had bcl-1 gene rearrangements in eight out of nine cases compared with three out of 10 cases of classic centrocytic lymphoma. DNA analysis was not able to detect bcl-2 gene rearrangement in any case, pointing to a difference compared with lymphomas of germinal centre origin. The coincidence of anaplastic and sometimes blast-like morphology of the tumour cells, high proliferation index and a rearranged bcl-1 gene in nearly all cases of anaplastic centrocytic lymphoma support their classification as high-grade malignant variants of centrocytic lymphoma and suggest a possible role for the bcl-1 locus not only in the origin but also in the progression of centrocytic lymphomas.     

Relevance of Ki-67 expression in the classification of non-Hodgkin''s lymphomas: a morphometric and double-immunostaining study

The proliferation of reactive and neoplastic cells was retrospectively assessed in 92 cases of non-Hodgkin's lymphoma by morphometry using a double-immunoenzymatic technique including surface markers and the monoclonal antibody Ki-67. The findings were compared with the histological diagnosis. The overall Ki-67 positivity is not always a good measure of the corresponding corrected values and therefore we recommend that a correction should be made for the total number of complementary lymphocytes in the tumour. Taking the macrophages and the Ki-67 positivity of the reactive cells into account does not generally add any information. There was no difference in reactive cell content between follicular (counted within follicles) and diffuse lymphomas within the tumour areas. The value of the group mean for low-grade follicular (nodular) lymphomas was significantly higher than that of diffuse low-grade lymphomas, but not significantly different from that of intermediate-grade lymphomas. High-grade lymphomas exhibited significantly greater Ki-67 positivity than those of intermediate grade. In 76% of the cases there was significant agreement between malignancy grade (low/intermediate malignant versus high malignant) at 45% corrected Ki-67 counts.     

P57和Ki-67在葡萄胎鉴别诊断中的作用

目的:探讨P57和Ki-67蛋白在完全性和部分性葡萄胎鉴别诊断中的作用.方法:分别收集正常胎盘绒毛、部分性葡萄胎和完全性葡萄胎石蜡标本各12例,应用免疫组织化学方法检测P57和Ki-67蛋白在这些病变中的分布及表达水平.结果:P57蛋白在正常绒毛及部分性葡萄胎组织中主要分布于绒毛的细胞滋养叶细胞及间质细胞,两组间阳性率...     

Hepatitis C virus-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in hepatocytes

We have established monoclonal antibodies (MoAbs) that are directed against hepatitis C virus (HCV)-expressing cells. They showed enhanced tumorigenicity after passage in culture for more than 44 days (RzM6-44d cells). To address the mechanism underlying this phenomenon, we characterized the MoAbs, and found that one of the clones recognized a molecule that was down-regulated in the RzM6-44d cells. This molecule was purified and identified as the 70-kDa thyroid autoantigen Ku70. Moreover, expression of the full-length HCV genome or HCV-core protein sequence in WRL68 human embryonic liver cells reduced the level of Ku70 protein, enhanced the ubiquitination of Ku70, and decreased the activity of DNA-activated protein kinase (DNA-PK). Therefore, it appears that the HCV-core protein facilitates the degradation of Ku70 and reduces DNA-PK activity in noncancerous liver cells.     

子宫内膜癌中Rb2/P130、PTEN及Ki-67的表达及意义

目的 探讨正常子宫内膜、子宫内膜增殖症及内膜癌组织中Rb2/P130、PTEN及Ki-67的表达以及与子宫内膜癌发生的关系.方法 应用免疫组化SP法检测30例正常子宫内膜组织、32例单纯型增生过长、31例复杂型增生过长、36例不典型增生、64例子宫内膜癌组织中Rb2/P130、PTEN和Ki-67的表达.结果 Rb2/P130、PTEN蛋白在正常子宫内膜、单纯性增生过长、复杂型增生、不典犁增生、子官内膜癌组织中的阳性表达率依次递减,而Ki-67的阳性表达率依次递增,子宫内膜癌和不典型性增生中Rb2/P130、PTEN阳性表达率明显低于正常增生期子宫内膜和单纯性增生,差异均有显著性(P均<0.01),而Ki-67的阳性表达率明显高于正常增牛期子宫内膜和单纯性增生过长,差异均有显著性(P均<0.01).Rb2/P130、PTEN阳性表达缺失与组织学分级有关(P均<0.01)、与子宫肌层浸润程度无关,Rb2/P130阳性表达缺失与淋巴结转移无关,PTEN阳性表达缺失与淋巴结转移有关(P<0.05),而Ki-67阳性表达与组织学分级、临床分期及淋巴结转移有关(P<0.01,P<0.05,P<0.01),与子宫肌层浸润程度无关.Rb2/P130、PTEN蛋白表达与Ki-67呈负相关(P<0.003.P<0.000).结论 Rb2/P130、PTEN蛋白与Ki-67的异常表达与子宫内膜癌的发生相关,有可能成为子宫内膜组织早期癌变的有用标记物.