联合检测子宫内膜样腺癌组织Ki-67、ER与CEA表达的临床诊断价值

目的探讨联合检测Ki-67、ER与CEA可否提高子宫内膜样腺癌的诊断和鉴别价值。方法采用免疫组织化学方法,对50例子宫内膜样腺癌和25例宫颈原发性腺癌组织检测Ki-67、ER与CEA,卡方检验分析两种类型腺癌组织的表达差异及各项指标之间的相关性,并统计比较Ki-67、ER与CEA三联检测和Ki-6与CEA两联检测的敏感性、特异性和准确度。结果在子宫内膜样腺癌组织中,ER和Ki-67的阳性表达率为82.0%和86.0%,明显高于宫颈腺癌组织,而CEA的表达低于宫颈腺癌组织,组间比较差异具有统计学意义(P0.05);在子宫内膜样腺癌组织中,在ER阳性组中Ki-67、CEA的阳性表达高于ER阴性组,两者呈正相关(P0.05)。三联检测诊断子宫内膜样腺癌的敏感性、特异性和准确度分别为65.3%、100%和80.2%,明显高于两联检测法(P0.05)。结论在子宫内膜样腺癌中存在明显的ER高表达,且与Ki-67、CEA的阳性表达呈负相关,在常规的Ki-67与CEA两项检测中加入ER可有效提高诊断的特异性和准确性,具有显著的临床价值。     

子宫内膜腺癌组织中cyclinD1、PCNA和Ki-67的表达

目的　探讨cyclinD1、PCNA和Ki 6 7在子宫内膜腺癌组织中的表达及其意义。 方法　采用免疫组化S P法检测正常增生期子宫内膜 10例、单纯性增生 30例、复杂性增生 30例、非典型增生 30例和子宫内膜腺癌 4 7例组织中cyclinD1、PCNA和Ki 6 7的表达。结果　cyclinD1在增生期子宫内膜组织中未见阳性表达 ,在单纯性增生、复杂性增生、非典型增生和子宫内膜腺癌组织中的阳性表达率分别为 13 3%、16 7%、30 0 %和 5 7 8%。非典型增生和子宫内膜腺癌组织阳性表达率高于增生期宫内膜、单纯性和复杂性增生 (P <0 0 5 ) ,cyclinD1蛋白表达与子宫内膜腺癌临床分期、肌层浸润和淋巴结转移呈正相关 (P<0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。PCNA和Ki 6 7在非典型增生组标记指数 (LI)高于增生期宫内膜、单纯性和复杂性增生组 ,子宫内膜腺癌组高于非典型增生组 (P <0 0 5 ) ,PCNA和Ki 6 7LI与肿瘤的分化程度、临床分期、肌层浸润和淋巴结转移呈正相关 (P <0 0 5 )。PCNA和Ki 6 7在cyclinD1阳性表达组的LI高于阴性组 (P <0 0 5 )。结论　cyclinD1蛋白过度表达可能在子宫内膜癌的发生、发展中起重要作用 ,其作用途径可能是通过促进细胞增殖而实现的。     

子宫内膜样腺癌组织中p53蛋白和VEGF的表达及意义

子宫内膜癌是最常见的女性生殖道恶性肿瘤之一,近年来子宫内膜癌的发病率有明显增高趋势,与宫颈癌收治率比较,已趋接近甚至超过,而与雌激素相关的子宫内膜样腺癌占全部子宫内膜癌的80％～900h,,其与子宫内膜增生过长关系密切。笔者运用免疫组化S-P法检测p53、VEGF在子宫内膜样腺癌中的表达,旨在探讨其与子宫内膜样腺癌的组织学分级、浸润深度、临床分期和肿瘤转移、预后的关系。     

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     

子宫内膜样腺癌中PLAGL1和ERβ的表达及临床意义

目的 探讨多形性腺瘤基因L1(pleomorphic adenoma gene like-1, PLAGL1)和雌激素受体(estrogen receptorβ, ERβ)在子宫内膜样腺癌(uterine endometrioid adenocarcinoma, UTEA)中的表达及两者与临床病理特征的关系。方法 筛选肿瘤基因组图谱(the Cancer Genome Atlas, TCGA)中子宫内膜癌(uterine corpus endometrial carcinoma, UCEC)及正常子宫内膜组织中的差异表达基因;采用UALCAN数据库分析PLAGL1和ESR2 mRNA在UCEC及正常组织中的表达。采用免疫组化法检测84例UTEA及43例癌旁正常子宫内膜中PLAGL1和ERβ表达,分析两者与UTEA临床病理特征的关系及相关性。结果 TCGA及UALCAN数据库分析显示：UCEC中PLAGL1 mRNA表达显著低于正常子宫内膜组织(P<0.01),而正常子宫内膜组织和UCEC中ESR2 mRNA的表达水平差异无统计学意义(P>0.05)。UTEA中PLAGL1高...     

子宫内膜样腺癌组织中PRRX1蛋白的表达及临床意义

目的探讨配对相关同源框1(paired related homoeobox 1,PRRX1)蛋白在子宫内膜样腺癌组织中的表达及临床意义。方法选取安徽医科大学第一附属医院以及安徽医科大学附属巢湖医院267例子宫内膜组织标本,其中正常子宫内膜86例,子宫内膜上皮内瘤变90例,子宫内膜样腺癌91例,均行免疫组化EliVision法检测,观察不同子宫内膜组织中PRRX1表达及子宫内膜样腺癌临床病理特征与PRRX1的关系。结果PRRX1蛋白表达主要定位于子宫内膜样腺癌组织的细胞核中,91例子宫内膜样腺癌组织中PRRX1阳性率为79.1%,高于正常子宫内膜组织(0)、子宫内膜上皮内瘤变组织(10.0%),差异有统计学意义(P<0.05)。子宫内膜样腺癌患者按FIGO分级分类,FIGO1级的PRRX1阳性率低于FIGO 2、3级,差异有统计学意义(P<0.05);按患者年龄、临床分期、有无淋巴结转移分组,PRRX1阳性率差异均无统计学意义(P>0.05)。结论子宫内膜样腺癌组织中的PRRX1表达量高,且与FIGO分级相关。     

子宫内膜样腺癌中ARID1A蛋白的表达及意义

目的探讨ARID1A蛋白表达与子宫内膜样腺癌发生、发展的关系。方法采用免疫组化SP法检测子宫内膜的增生期、分泌期、孕期、简单性增生、复杂性增生、不典型增生和子宫内膜样腺癌中ARID1A蛋白的表达,分析其表达与临床病理特征及生存期的相关性。结果子宫内膜的增生期、分泌期、孕期、简单性增生及复杂性增生组织中ARID1A蛋白均呈阳性;子宫内膜不典型增生和子宫内膜样腺癌组织中ARID1A蛋白缺失率分别为8.33%(3/36)和41.51%(44/106),较不伴不典型增生的子宫内膜显著升高,子宫内膜样腺癌的ARID1A蛋白缺失率较不典型增生显著升高(χ2=13.358,P0.01);子宫内膜样腺癌的ARID1A蛋白缺失率与病理组织学分级呈负相关(P0.05)。ARID1A蛋白缺失率与患者年龄、是否绝经、子宫体肌层浸润深度、FIGO分期、淋巴结转移及生存期无关。结论 ARID1A蛋白缺失是子宫内膜样腺癌发生的早期事件,在子宫内膜样腺癌发生过程中具有重要作用,而对子宫内膜样腺癌进展的作用不明显。     

子宫内膜样腺癌及癌前病变组织中PTEN、cyclin E蛋白的表达

肿瘤的本质在于细胞周期调节机制失控,导致细胞异常增殖所致。我们采用免疫组化技术检测子宫内膜样腺癌及癌前病变组织中的PTEN和cyclin E蛋白,探讨其在子宫内膜样腺癌发生、发展中的作用及与临床病理特征之间的关系。1材料与方法1.1病例来源选自本院1996年6月~2002年6月的子宫内膜病变标本,其中子宫内膜增生组30例(18例为单纯性、12例为复杂性)、子宫内膜不典型性增生组20例,子宫内膜样腺癌组55例,另取30例正常子宫内膜标本为对照组。55例子宫内膜样腺癌中随访45例,至2005年12月,其中11例(24·4%)肿瘤复发。1.2方法免疫组化染色采用SP法…     

前列腺腺癌中双染鸡尾酒抗体Ki-67/caspase-3的表达及意义

目的探讨Ki-67/caspase-3鸡尾酒抗体在前列腺腺癌(PAC)、高级别前列腺上皮内瘤(HGPIN)及良性前列腺增生(BPH)组织中的表达及意义。方法收集40例PAC、30例HGPIN和BPH标本,按常规方法石蜡包埋,制作蜡块连续切片,进行HE染色及Ki-67/caspase-3鸡尾酒抗体双重免疫组化染色。结果 Ki-67表达阳性率及增殖指数在PAC组织中明显高于HGPIN和BPH组织,且随着Gleason分级增高其增殖指数存在递增趋势(P0.05,P0.01)。caspase-3在BPH组织中表达阳性率明显高于PAC及HGPIN组织(P0.05),但在PAC与HGPIN、不同Gleason分级PAC中的表达阳性率差异无统计学意义(P0.05)。Ki-67和caspase-3在PAC和HGPIN组织中的表达呈负相关,而在BPH中的表达呈正相关。结论 Ki-67/caspase-3在不同病变中表达不同,鸡尾酒抗体联合检测可用于前列腺良恶性疾病的诊断、鉴别诊断及预后的判断。     

子宫内膜样腺癌中mTOR和eIF4E蛋白表达及临床意义

目的 探讨mTOR和eIF4E蛋白在子宫内膜样腺癌发生中的作用和临床意义.方法 采用免疫组化EliVision方法分别检测17例增殖期宫内膜、64例子宫内膜增生性病变和44例子宫内膜样腺癌中mTOR和eIF4E蛋白的表达情况.结果 mTOR在增殖期子宫内膜和单纯性增生宫内膜中均无强阳性表达,复杂性增生宫内膜和子宫内膜样腺癌中mTOR强阳性表达率分别为23.40%和52.27% ,明显高于增殖期子宫内膜和单纯性增生宫内膜(P<0.05).子宫内膜样腺癌中mTOR的强阳性表达率明显高于复杂性增生宫内膜和复杂性非典型增生中的宫内膜(P<0.05).子宫内膜样腺癌中mTOR强阳性表达与肿瘤分化程度密切相关,Ⅱ、Ⅲ级子宫内膜样腺癌的强阳性表达率明显高于Ⅰ级(72.41% vs 13.33%,P<0.05).而与TNM分期和淋巴结转移均无相关性(P>0.05).eIF4E蛋白在增殖期宫内膜,单纯性增生宫内膜,复杂性增生宫内膜,子宫内膜样腺癌中的阳性表达率分别为52.94%,73.68%,85.11%和90.91%.复杂性增生宫内膜和子宫内膜样腺癌中eIF4E蛋白的阳性表达均明显高于其它各组(P<0.05),但两者差异无显著性(P>0.05).eIF4E与子宫内膜样腺癌分化程度、TNM分期和有无淋巴结转移均无相关性(P>0.05).结论 mTOR、eIF4E蛋白在复杂性增生宫内膜和子宫内膜样腺癌中表达明显增强,提示两者可能在子宫内膜样腺癌发生中发挥一定作用.     

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.     

Ki-67 derived proliferative activity in colorectal adenocarcinoma with prognostic correlations

Cryostat sections from samples of 108 colorectal carcinomas were stained with the murine monoclonal antibody Ki-67, which is expressed in proliferating cells. Ki-67 immunoreactivity was assessed independently by two pathologists using a semi-quantitative method. There was excellent correlation between the two observers. Ten cases were assessed quantitatively by counting at least 2000 cells and there was a very good correlation between this method and the semi-quantitative method. The carcinomas showed a wide range of Ki-67 labelling, reflecting a variation in proliferative activity. The tumour labelling index ranged from 1 to 80 per cent positivity: there was also heterogeneity of labelling within many of the tumours. There was no correlation between Ki-67 derived proliferative score and known prognostic parameters, including Dukes stage, New Prognostic Classification grade, lymph node status, tumour differentiation, venous spread, invasive margin, lymphocytic infiltrate, and curative versus palliative surgery. Nevertheless, it is concluded that Ki-67 immunohistochemistry provides a reliable and reproducible method of assessment of proliferative activity in colorectal cancer. Ki-67 immunohistochemistry may have a clinical application in the selection of patients with colorectal cancers who might benefit from radiotherapy and/or chemotherapy, particularly those with unresectable or locally recurrent tumours.     

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.     

浸润性乳腺癌及转移淋巴结中RKIP和Ki-67的表达及意义

目的 探讨RKIP和Ki-67在浸润性乳腺癌及其淋巴结转移灶中的表达及意义.方法 应用免疫组化SP法检测RKIP和Ki-67在52例浸润性乳腺癌及其淋巴结转移灶中的表达情况.结果 乳腺癌淋巴结转移灶与原发灶相比,RKIP表达水平明显下降,两者之间有统计学差异(P<0.01).Ki-67指数在乳腺癌淋巴结转移灶明显高于原发灶(P<0.01);但RKIP与Ki-67之间,无论是原发灶,还是转移灶,都无相关关系(均P>0.05).结论 RKIP具有抑制浸润性乳腺癌转移的作用,属于转移抑制基因;Ki-67可反映乳腺癌的增殖活性及转移和预后,但RKIP的表达对乳腺癌细胞的增殖无明显影响.     

Proliferative activity as revealed by Ki-67 in uterine adenocarcinoma of endometrioid type: Comparison of tumours from patients with and without previous oestrogen therapy

The Ki-67 antibody recognizes a nuclear antigen related to cell proliferation, which in some studies has been shown to reflect the aggressiveness of tumours. The percentage of Ki-67-positive cells was estimated by immunohistochemistry on frozen tissue sections from 73 adenocarcinomas of endometrioid type (EC) (40 tumours from patients who had never received postmenopausai oestrogen treatment and 33 tumours from patients with previous postmenopausal oestrogen treatment). The Ki-67 content was weakly but significantly (P<0.05) correlated to nuclear grade, architectural grade, and crude mitotic count, but not to stage or progesterone receptors. Ki-67 expression in EC from patients with previous oestrogen therapy was much lower (median 10 per cent Ki-67) than that in EC from patients who had never received oestrogen treatment (median 24 per cent Ki-67), suggesting that a prognostic cut-off point may be different in tumours from the two groups of patients. The mitotic count discriminated the two groups of patients to a much smaller degree. It is also shown that a quick qualitative Ki-67 estimate can replace the time-consuming quantitative assessment.     

Prognostic significance of the infiltrative pattern invasion in endometrioid adenocarcinoma of the endometrium

The prognostic significance of the invasive type of carcinoma cells in endometrial carcinoma is not defined. We evaluated the prognostic significance of the invasive type, as well as the immunostains of p53, c-erbB-2, Ki-67 antigen and MDM2 in endometrial endometrioid adenocarcinoma. This prospective analysis comprised 112 patients with endometrioid adenocarcinoma of the uterine corpus who had undergone surgery and were traced for more than 5 years after the operation. They were divided into recurrence (16 patients) and non-recurrence (96 patients) groups. The invasive type of carcinoma cells was divided into expansile, mixed (expansile and infiltrative) and infiltrative pattern. The difference in the invasive type (P < 0.001) and p53 expression (P = 0.004) between the recurrence and non-recurrence groups was significant in the univariate analysis. Moreover, the invasive type was significant in the multivariate analysis (P = 0.004). In contrast, the difference in MDM2 expression, c-erbB-2 expression and the Ki-67 labeling index in both groups was not significant in the univariate analysis. The infiltrative pattern of the invasive type (P < 0.001) and p53 expression (P = 0.043) were significantly related to a poor prognosis in the Kaplan-Meier method using the log-rank test. In conclusion, the current study indicated that the infiltrative pattern of the carcinoma cells is a predictor for poor prognosis in endometrioid adenocarcinoma in the uterine corpus. It was also indicated that p53 immunostains are useful as a predictor, but Ki-67 antigen, c-erbB-2 and MDM2 stains are not.     

宫颈与宫体子宫内膜样腺癌的临床病理及免疫表型分析

目的探讨宫颈子宫内膜样腺癌和宫体子宫内膜样腺癌的临床病理和免疫表型差异。方法采用HE及免疫组化En-Vision两步法对8例宫颈内膜样腺癌和76例宫体内膜样腺癌的组织学形态和免疫表型进行比较观察。结果宫颈子宫内膜样腺癌和宫体子宫内膜样腺癌在组织学形态上相似。两组标本的免疫标记物阳性率分别为vimentin(0,95.45%)、CEA(100%,45.45%)、p53(12.50%,31.82%)、ER(0,54.54%)、PR(0,60.61%)、Ki-67(75.0%,12.12%)、HPV16/18(100%,3.03%)、p16(100%,46.97%)、Cam5.2(12.50%,62.12%)。两者相比,vimentin、CEA、ER、PR、p16、Ki-67、HPV16/18、PAS、Cam5.2的表达差异有显著性(P<0.05),而p53的表达差异无统计学意义(P>0.05)。结论应用免疫标记物vimentin、CEA、ER、PR、p16、Ki-67、HPV16/18、PAS、Cam5.2检测是鉴别宫颈和宫体子宫内膜样腺癌的一种重要的有效方法,p53可作为辅助鉴别的免疫标记物。     

The utility of Ki-67 expression in the differential diagnosis of prostatic intraepithelial neoplasia and ductal adenocarcinoma

Cribriform and/or papillary prostatic lesions observed on limited tissue, such as needle biopsy, can pose diagnostic dilemmas. One such area of difficulty is the distinction between papillary and/or cribriform prostatic high-grade prostatic intraepithelial neoplasia (HG-PIN) and ductal adenocarcinoma. Over 48 months, we identified 17 cases of ductal adenocarcinoma and 17 cases of HG-PIN from radical retropubic prostatectomy specimens. The HG-PIN lesions were in all cases associated with an acinar prostatic adenocarcinoma component. For each case, we evaluated the proliferative activity, assessed by Ki-67 immunohistochemistry. The majority (82%) of ductal adenocarcinomas were composed of mixed papillary and cribriform patterns, with the remaining demonstrating pure papillary or cribriform patterns. The HG-PIN lesions showed a papillary, cribriform, or mixed papillary/cribriform architecture. The proliferative activity, defined as Ki-67 labeling index, was statistically higher in ductal adenocarcinoma (mean 33%, range 21%-66%) as compared with HG-PIN (mean 6%, range 2%-15%), with no overlap in the Ki-67 indices (P = 0001). A combination of histological features and measurements of cellular proliferation may be helpful to distinguish HG-PIN from ductal adenocarcinoma in limited prostatic tissue samples.