Ki-67在早期乳腺癌诊治中的意义

早期乳腺癌(EBC)的预后差异非常大,重要的预后因素有肿瘤大小、组织学分级、脉管浸润情况、淋巴结转移情况等是有所帮助的,肿瘤的分子特征也正受到越来越多的关注,ER、Her-2已经被作为治疗反应和预后的预测指标.Ki-67虽然不作为必须的标记,但常用来作为增殖活性的静态标志,或通过治疗期间的多次测量,来反映动态变化的中间状态,以及作为疗效的替代指标.现应就Ki-67在早期乳腺癌的预后和治疗的预测价值作一综述.     

Ki-67及PTEN在口腔腺样囊性癌中的表达及临床意义

目的 研究口腔腺样囊性癌(OACC)中Ki-67和PTEN的表达情况,及其表达水平与临床病理特征的关系。方法 收集佳木斯大学附属第一医院病理实验室证实的40例口腔腺样囊性癌。另选口腔腺样囊性癌患者标本癌旁正常腺体15例做对照组。免疫组化SP法检测腺样囊性癌中Ki-67蛋白及PTEN的表达。结果 Ki-67蛋白在口腔腺样囊性癌中的阳性率为70%(28/40),明显高于对照组13%(2/15)(P＜0.05)。PTEN蛋白在口腔腺样囊性癌中的阳性率为63%(25/40),明显高于对照组20%(3/15)(P＜0.05)。Ki-67、PTEN的表达与TNM分期、肿瘤组织学类型、远处转移、淋巴结转移和神经节浸润均显著相关,并且Ki-67和PTEN表达存在相关性。结论 Ki-67和PTEN在口腔腺样囊性癌发生和发展过程中可能起重要作用。Ki-67和PTEN蛋白可能作为口腔腺样囊性癌的诊断标志物。     

Proliferation marker Ki-67 in early breast cancer.

Molecular markers have been extensively investigated with a view to providing early and accurate information on long-term outcome and prediction of response to treatment of early breast cancer. Proliferation is a key feature of the progression of tumors and is now widely estimated by the immunohistochemical assessment of the nuclear antigen Ki-67. The expression of Ki-67 correlates with other measurements of proliferation, including S-phase and bromodeoxyuridine uptake. High Ki-67 is a sign of poor prognosis associated with a good chance of clinical response to chemotherapy, but its independent significance is modest and does not merit measurements in most routine clinical scenarios. However, its application as a pharmacodynamic intermediate marker of the effectiveness of medical therapy holds great promise for rapid evaluation of new drugs.     

Comparative analysis of [3H]-thymidine labelling index and monoclonal antibody Ki-67 in non-Hodgkin's lymphomas

The relation between the [³H]-thymidine labelling index (3H-Thy LI), which evaluates the S-phase cells, and the monoclonal antibody Ki-67 (MoAb Ki-67), which recognizes a nuclear antigen expressed during the cell cycle, was defined in 35 non-Hodgkin's lymphomas (NHL). Significantly higher median values of [³H]-Thy LI and Ki-67-positive cells were observed for high-grade than for low-grade malignancy tumours according to the Kiel classification, but with wide and overlapping values for the two morphologic subgroups. A significant correlation was observed between [³H]-Thy LI and Ki-67-positive cells (P < 0.0001; r = 0.62). However, the ratio between the two cell kinetic variables on individual tumours was not constant. It sharply increased with decreasing [³H]-Thy LI values and was much higher in low-grade NHL than in high-grade NHL. Follow-up studies are needed to establish the role of the tumour growth fraction as evaluated by MoAb Ki-67 as a prognostic indicator in NHL.     

Ki-67、p53蛋白在乳腺癌组织的表达及临床意义

目的探讨Ki-67、p53蛋白在乳腺癌及癌旁组织中的表达及两者之间的关系和临床意义。方法应用免疫组化S-P法检测80例乳腺癌组织及其癌旁的正常乳腺组织中Ki-67、p53蛋白的表达,分析其与临床病理因素的关系及两者的相关性。结果80例乳腺癌组织中Ki-67蛋白阳性表达率为63.8%,高于癌旁乳腺组织8.8%（P〈0.05）,其表达与患者年龄、肿瘤大小、ER、PR表达无关,与肿瘤的分期、腋窝淋巴结转移、C-erbB-2表达相关。乳腺癌组织p53蛋白阳性表达率为68.8%,高于癌旁乳腺组织11.3%（（P〈0.05）,其表达与年龄、肿瘤大小、分期、ER、PR表达无关,与腋窝淋巴结转移、C-erbB-2表达相关。Ki-67蛋白与p53蛋白表达之间无关。结论Ki-67、p53蛋白可通过抑制细胞凋亡,对乳腺癌发生和发展起重要作用,是判断乳腺癌生物学行为、预测转移趋势有价值的参考指标。     

急性髓系白血病Ki-67的表达及其临床意义

目的：探讨增殖相关抗原Ki-67在急性髓系白血病（AML）中的表达及其临床意义。方法选取2012年10月至2016年1月首都医科大学附属复兴医院血液内科住院AML患者45例,其中初治36例,复发9例;以20例健康志愿者作为健康对照。采用流式细胞术（FCM）检测骨髓原始细胞群Ki-67抗原的表达,分析Ki-67水平与患者临床特征的相关性。结果初治、复发AML患者和健康对照者的骨髓原始细胞群Ki-67阳性率分别为（10.38±8.41）%、（20.99±11.49）%和（40.77±11.97）%,初治和复发AML患者的Ki-67阳性率均低于健康对照者（均P＜0.05）,初治AML患者Ki-67阳性率低于复发AML患者（P＝0.006）。初治AML患者的Ki-67水平与患者的年龄、FAB亚型、白细胞计数、有无骨髓增生异常综合征（MDS）病史、乳酸脱氢酶水平、骨髓原始细胞比例、NPM1基因突变、FLT3内部串联重复（ITD）、染色体核型、诱导化疗反应均无关（均P＞0.05）。初治AML患者Ki-67高水平组与低水平组的总生存时间分别为（780±110）d和（788±118）d,两组差异无统计学意义（P＝0.927）。结论 AML患者原始细胞群增殖活性较健康对照低,检测Ki-67水平可能为临床选择细胞周期特异性化疗药物提供依据;对AML患者动态监测Ki-67水平有助于监测疾病进展,预测复发。     

Determination of the proliferative fraction of a transplantable, hormone-dependent, human prostatic carcinoma (PC-82) by monoclonal antibody Ki-67: potential application for hormone therapy monitoring

The transplantable, hormone-dependent, human prostatic carcinoma PC-82 was used as an in vivo model for monitoring the proliferative fraction of tumor cells under the influence of androgen withdrawal and resubstitution. The number of cycling cells was assessed by means of an immunoperoxidase method and monoclonal antibody Ki-67. The number of Ki-67-positive tumor cells dropped from an average of 17% in androgen-supplemented, tumor-bearing female BALB/c mice to approximately 1.0% within 10 days after removal of the testosterone (T) implant. A similar effect was noted after castration of tumor-bearing male BALB/c mice. Androgen resubstitution after a 10-day period of T deprivation resulted in a rise in the tumor cell proliferation index to 20% within 4 days. The same pattern of response to androgen depletion and resubstitution also was found when the number of cycling cells in S phase was assessed by the 5-bromo-2'-deoxyuridine incorporation technique. Administration of supraphysiologic doses of T in intact male mice did not lead to an increase in the number of Ki-67-stained nuclei. Androgen manipulation did not influence the immunohistochemically assessed expression of prostatic acid phosphatase and prostate-specific antigen. The rapid effect of hormone deprivation and resubstitution in the tumor cell proliferation fraction suggests that monoclonal antibody Ki-67 can be used for monitoring the short-term effects of hormonal treatment of prostatic cancer.     

Immunohistochemical evaluation of growth fractions in human breast cancers using monoclonal antibody Ki-67

Summary We performed immunohistochemical analyses of 568 breast/cancer specimens using Ki-67, a monoclonal antibody specific for a nuclear antigen present in proliferating cells. The specimens were divided into three groups (I–III) according to the proportion of Ki-positive cells detected. These findings were compared with features of tumor extension as well as with certain prognostic variables.There was no detectable correlation between Ki-67 reactivity and either tumor size or node involvement. In contrast, a statistically significant correlation was found between Ki-67 reactivity and tumor grading, in that G-I tumors had small growth fractions, while a high proportion of G-III tumors exhibited strong (group III) Ki-67 positivity. When growth fractions were compared with biochemical receptor status, a significant difference was detected between tumors with negative and positive findings for receptors. The same co-variation was observed with respect to the overexpression ofneu-protein P185, with mostneu-positive carcinomas being strongly positive for Ki-67 (group III).In the relapse cases examined, there was a close correspondence between Ki-67 reactivity and the duration of the disease-free period. Long-term observation of patients with primary breast carcinoma revealed that, with regard to overall survival, the less reactive groups I and II differed significantly from group III. With respect to disease-free survival, no difference was detectable between Ki-groups II and III, but when these two groups together were compared with group I, a significant trend emerged. Similar results for both overall and disease-free survival were obtained for subgroups of pT2 and G-II carcinomas as well as for receptor expression. Node-negative tumors in the highly reactive group III exhibited a strong trend indicating unfavorable overall survival rates, whereas no such difference was demonstrable with respect to disease-free survival. Node-positive tumors could not be differentiated on the basis of overall survival, but the correlation with growth fraction was significant for disease-free survival.In conclusion, Ki-67 offers a simple and effective method for defining the proliferating cell compartment of breast carcinoma, and may facilitate the assessment of individual tumors as well as efforts to predict the course of disease.     

Ki-67在T1期非肌层浸润性膀胱癌中的表达及意义

  目的   检测Ki-67在T1期非肌层浸润性膀胱癌（non-muscle invasive bladder cancer,NMIBC）组织中的表达,并探讨其与肿瘤复发和进展的关系。   方法   回顾性分析2011年6月至2013年10月天津医科大学肿瘤医院102例T1期NMIBC患者的临床病理资料,利用免疫组织化学方法检测组织中Ki-67的表达,分析Ki-67表达与患者临床病理特征的关系,探讨其对T1期NMIBC复发和进展的影响。   结果   中位随访时间43（24~57）个月,102例T1期NMIBC患者中20例（19.6%）复发,12例（11.8%）进展,32例（31.4%）Ki-67表达≥25%。Ki-67表达与肿瘤分级相关（P < 0.05）,与患者性别、年龄、肿瘤数目、肿瘤大小等无相关性（P > 0.05）。单因素分析结果显示,Ki-67表达与T1期NMIBC的复发无相关性（P > 0.05）,Ki-67表达、肿瘤分级、肿瘤数目和既往复发率是影响T1期NMIBC进展的危险因素（P < 0.05）,Cox风险回归模型多因素分析结果显示,Ki-67高表达（P=0.043）和既往复发率（P=0.018）是影响T1期NMIBC进展的独立危险因素。   结论   Ki-67表达是T1期NMIBC的独立预后因素,检测Ki-67表达有助于预测其进展风险,为采取及时有效治疗提供依据。      

Proliferation in non-Hodgkin's lymphomas as determined by immunohistochemical double staining for Ki-67.

The authors have studied proliferation (growth fractions) in non-Hodgkin's lymphomas (NHL) using an immunohistochemical double staining technique with the monoclonal antibody (MoAb), Ki-67, in order to clarify the relationships between histologic type, proliferation and prognosis. The percentages of Ki-67 positive (Ki-67+) cells in B cell lymphomas were higher for diffuse lymphomas than for follicular lymphomas and increased in order from small to large cell types. In addition, the percentage of Ki-67+ cells in B cell lymphomas inversely correlated with survival in months (n = 33 r = -0.54 p < 0.01). These results indicate that the percentage of Ki-67+ cells in B cell lymphomas correlates with histologic type and prognosis. Although the prognosis of T cell lymphomas is considered worse than that of B cell lymphomas, the percentage of Ki-67+ cells was lower, in general, in T cell lymphomas than in B cell lymphomas. These data indicate that proliferation in T cell lymphomas does not correlate with survival.     

Proliferation index in various stages of breast cancer determined by Ki-67 immunostaining.

To investigate factors involved in progression of breast cancer, we estimated the growth fraction of malignant cell populations in various stages of mammary cancer growth. Frozen sections were immunostained with the Ki-67 monoclonal antibody and the proliferation index determined using static image analysis. Pure intraductal carcinoma, intraductal carcinoma coexisting with invasive disease, and metastatic sites coexisting with primary tumors were studied. The proliferation index of pure intraductal carcinomas (mean 4.5%, median 1.8%) was not significantly different from invasive mammary cancers (mean 5.1%, median 2.2%). The proliferation index determined for the in situ component of primary cancers (mean 3.8%, median 1.5%) was not significantly different from values obtained from the invasive component of growth (mean 4.2%, median 2.1%). Variability between in situ and invasive components for individual cases was minimal in tumors whose proliferation index was less than 3.0%; for tumors with higher proliferation indices, the differences were greater. However, there was no trend toward a decrease or increase in growth fraction for the two components of primary tumor growth. The mean proliferative index for primary tumors (mean 4.9%, median 4.0%) was not significantly different from the mean proliferative score from a matched group of metastatic sites in the same patients (mean 5.7%, median 5.5%). Comparison of individual cases uncovered differences in some tumors; again no consistent trends in either direction were noted. An increase (or decrease) in growth activity does not accompany the transition from intraductal (in situ) disease to invasive mammary cancer, nor does a change in growth fraction necessarily accompany progression of mammary cancer from the primary to regional metastatic site.     

Ki-67抗原在膀胱癌中的表达及其意义

目的探讨Ki-67抗原在膀胱癌中的表达及其与膀胱癌分级、分期的关系。方法采用免疫组织化学法检测Ki-67抗原在60例膀胱癌患者和20例膀胱良性病变和10例正常膀胱黏膜中的表达。结果Ki-67抗原在60例膀胱癌标记指数为25．9％,在20例膀胱良性病变为103％,在10例正常膀胱黏膜中为1．1％,各组间差异有统计学意义;Ki-67抗原随着膀胱癌病理分级和临床分期的增加而表达升高。结论Ki-67抗原在膀胱癌细胞中表达升高并与膀胱癌分期、分级密切有关,Ki-67的表达可以作为评价细胞增生状态的指标,有可能成为判断肿瘤发生、发展、预后的重要指标。     

肾细胞癌E-cad和Ki-67的表达情况及其临床意义

目的：观察肾癌组织中E-cad和Ki-67表达情况及其与临床、病理关系,探讨其在肾癌发生、发展中的作用。方法：应用免疫组织化学技术（SP方法）测定43例肾癌患者癌组织标本中E-cad和Ki-67的表达,并分析其表达情况与肿瘤的生物学行为的关系。结果：肾癌中E-cad和Ki-67阳性表达率分别为23.2%和39.5%,正常肾组织阳性表达分别为63%和0。二者阳性表达均与肿瘤分期、临床分级密切相关（P〈0.05）,与其他临床病理参数之间无相关性。在肾癌中E-cad和Ki-67蛋白阳性表达具有密切相关性（P〈0.01）。结论：肾癌E-cad和Ki-67表达与其发生、发展密切相关。联合检测对肾癌患者预后及术后治疗有一定实用价值。     

肾细胞癌E-cad和Ki-67的表达情况及其临床意义

目的:观察肾癌组织中E-cad和Ki-67表达情况及其与临床、病理关系,探讨其在肾癌发生、发展中的作用.方法:应用免疫组织化学技术(SP方法)测定43例肾癌患者癌组织标本中E-cad和Ki-67的表达,并分析其表达情况与肿瘤的生物学行为的关系.结果:肾癌中E-cad和Ki-67阳性表达率分别为23.2%和39.5%,正常肾组织阳性表达分别为63%和0.二者阳性表达均与肿瘤分期、临床分级密切相关(P<0.05),与其他临床病理参数之间无相关性.在肾癌中E-cad和Ki-67蛋白阳性表达具有密切相关性(P<0.01).结论:肾癌E-cad和Ki-67表达与其发生、发展密切相关.联合检测对肾癌患者预后及术后治疗有一定实用价值.     

VEGF与Ki-67在甲状腺乳头状癌中的表达及临床意义

目的:探讨甲状腺乳头状癌组织中VEGF、Ki-67蛋白表达与其临床病理的关系。方法:应用免疫组化SP法,对55例甲状腺乳头状癌组织中VEGF、Ki-67蛋白进行检测。结果:甲状腺乳头状癌组VEGF蛋白阳性表达率为52.7%(29/55),Ki-67增殖指数为(11.07±3.84)%。VEGF蛋白的阳性率、Ki-67增殖指数随着肿瘤分化程度降低、淋巴结转移、被膜的侵犯逐渐增加。结论:VEGF、Ki-67蛋白表达异常可能在甲状腺乳头状癌发生或发展中起一定作用。VEGF、Ki-67蛋白的联合检测对甲状腺乳头状癌的早期诊断、预后的判断及对制定合理治疗方案有重要的临床应用价值。     

前列腺癌组织Ki-67表达及其临床意义的研究

目的:探讨核增殖抗原Ki-67在前列腺癌组织中的表达及其对临床的意义。方法:应用免疫组化SP法检测64例前列腺癌和81例前列腺增生手术或活检标本中Ki-67的表达情况。结果:64例前列腺癌组织中Ki-67表达有40例,81例前列腺增生中Ki-67表达有8例,其灵敏度63%,特异性90%,两组比较差异有统计学意义,χ2=40.05,P<0.005;前列腺癌各临床分期的Ki-67表达也不同,A、B期与C、D期比较差异也有统计学意义,χ2=21.12,P<0.005。结论:Ki-67可作为前列腺增生与前列腺癌的鉴别、前列腺癌的临床分期以及预后判断的一种新的重要参考指标。     

VEGF与Ki-67在甲状腺乳头状癌中的表达及临床意义

目的：探讨甲状腺乳头状癌组织中VEGF、Ki-67蛋白表达与其临床病理的关系。方法：应用免疫组化SP法,对55例甲状腺乳头状癌组织中VEGF、Ki-67蛋白进行检测。结果：甲状腺乳头状癌组VEGF蛋白阳性表达率为52.7%（29/55）,Ki-67增殖指数为（11.07±3.84）%。VEGF蛋白的阳性率、Ki-67增殖指数随着肿瘤分化程度降低、淋巴结转移、被膜的侵犯逐渐增加。结论：VEGF、Ki-67蛋白表达异常可能在甲状腺乳头状癌发生或发展中起一定作用。VEGF、Ki-67蛋白的联合检测对甲状腺乳头状癌的早期诊断、预后的判断及对制定合理治疗方案有重要的临床应用价值。