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1.
MGMT和Ki-67抗原在肝细胞癌组织中的表达及意义   总被引:1,自引:0,他引:1  
目的 探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)和细胞增殖核抗原Ki-67在原发性肝细胞肝癌(HCC)组织中的表达及意义.方法 应用免疫组化S-P法检测68例HCC组织及癌旁组织中MGMT及Ki-67抗原的表达.结果 MGMT、Ki-67抗原在HCc组织中的表达率分别为44.12%(30/68)和57.35%(39/68),MGMT的表达与Hcc组织病理分级有关(P<0.05),与其它临床因素无关(P>0.05);Ki-67抗原的表达与HCC的肿瘤大小、包膜是否完整、脉管有无癌栓、病理分级有关(P<0.05),与血清AFP的浓度无关(P>0.05);并且随Ki-67抗原表达强度的增加,MGMT的表达强度明显下降,Ki-67抗原与MGMT表达呈负相关(γ=-0.301,P<0.05).结论 MGMT在HCC的发生发展中可能起抑制作用,MGMT的缺失是HCC发生的重要分子事件之一,检测Ki-67抗原有助于判断HCC恶性程度及复发转移的风险,联合检测MGMT和Ki-67抗原有助于预测HCC患者预后.  相似文献   

2.
人脑胶质母细胞瘤Ki-67抗原表达及其预后作用   总被引:2,自引:0,他引:2  
目的探讨Ki-67抗原在人脑胶质母细胞瘤中的表达及其预后作用.方法使用S-P免疫组化方法检测31例人脑胶质母细胞瘤标本中Ki-67抗原的表达.单因素使用Kaplan-Meier法,多因素分析使用COX比例风险模型进行预后分析.结果Ki-67LI为(8.07±3.84)%.单因素及多因素分析均显示Ki-67指数是独立的预后因素.Ki-67指数≤2.5%与>2.5%的患者生存期分别为(46.17±17.21)月、(12.43±5.01)月,P<0.01.结论在人脑胶质母细胞瘤中,Ki-67指数不同,其预后也有显著不同.Ki-67指数>2.5%提示预后较差.  相似文献   

3.
目的:探讨人脑胶质瘤组织中O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)、表皮生长因子受体(EGFR)和细胞增殖相关核蛋白Ki-67的表达及其相关性。方法:选取64例脑胶质瘤组织标本,采用免疫组织化学染色法检测MGMT、EGFR及Ki-67的表达。结果:MGMT、EGFR、Ki-67总体阳性率分别为76.6%、59.4%和56.3%。在Ⅰ、Ⅱ、Ⅲ、Ⅳ级胶质瘤中,MGMT阳性表达率分别为0、58.8%、70.0%和100.0%;EGFR阳性表达率分别0、41.2%、60.0%和76.0%;Ki-67阳性表达率分别为0、23.5%、65.0%和76.0%。MGMT、EGFR和Ki-67的阳性表达率在脑胶质瘤不同病理分级间差异有统计学意义,P值分别为0.001、0.043和0.002;且三者的表达强度与胶质瘤病理分级呈正相关性,r值分别为0.315、0.273和0.400,P值分别为0.011、0.029和0.001。3种检测指标的阳性表达率与发病年龄及性别均无明显的相关性,差异无统计学意义,P>0.05。分层分析发现,Ki-67的表达与MGMT和EGFR的表达有相关性,r分别为0.296和0.466,P值分别为0.018和0.000。结论:人脑胶质瘤中MGMT、EGFR及Ki-67的表达与病理分级均有相关性,测定三者的表达水平可评价胶质瘤细胞的恶性程度,对胶质瘤预后判断可能有指导作用。  相似文献   

4.
Huang L  Jiang T  Yuan F  Li GL  Xu LX  Cui Y 《中华肿瘤杂志》2011,33(10):752-758
目的 探讨胶质瘤染色体1p和19q杂合性缺失(LOH)与O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)、p53和Ki-67蛋白表达的关系.方法 采集146例胶质瘤(45例少突胶质细胞瘤、42例少突星形细胞瘤和59例星形细胞瘤)的肿瘤组织和血液标本,采用聚合酶链反应结合变性高效液相色谱技术检测染色体1p和19q LOH,免疫组化法检测肿瘤组织中MGMT、p53和Ki-67蛋白的表达,并进一步分析其与胶质瘤临床病理特征的关系.结果 少突胶质细胞肿瘤和星形细胞瘤中,1p LOH的发生率分别为59.8%和33.9%,差异有统计学意义(P=0.002);1p和19q LOH的发生率分别为42.5%和16.9%,差异有统计学意义(P=0.001).MGMT低表达和Ki-67高表达多发生于少突胶质细胞肿瘤中,发生率分别为65.5%和54.0%,而p53高表达多发生于星形细胞瘤和少突星形细胞瘤中,发生率为75.2%.在87例少突胶质细胞肿瘤中,1p LOH和MGMT蛋白低表达多发生于Ⅱ级少突胶质细胞肿瘤中,发生率分别为72.5%和87.5%,而p53和Ki-67蛋白高表达多发生于Ⅲ级少突胶质细胞肿瘤中,发生率分别为83.0%和76.6%.1p和19q LOH在非颞叶和颞叶肿瘤的发生率分别为55.6%和21.2%(P=0.002).1p LOH与19q LOH、MGMT蛋白表达与p53蛋白表达、MGMT蛋白表达与Ki-67蛋白表达、1p和19q LOH与p53蛋白表达、1p LOH与Ki-67蛋白表达均有关(均P<0.05).结论 1p和19q LOH及MGMT、p53和Ki-67的蛋白表达与胶质瘤的临床病理学特征有关,检测其LOH状态和表达水平对胶质瘤的诊断和治疗具有指导作用.  相似文献   

5.
目的:通过检测肿瘤组织中O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的表达,探讨其与胃肠胰神经内分泌瘤以替莫唑胺为基础化疗患者预后的相关性。方法:收集2017年至2019年在我院接受替莫唑胺联合替吉奥化疗的15例晚期胃肠胰神经内分泌瘤患者的肿瘤组织,采用免疫组织化学法检测肿瘤组织中MGMT蛋白表达情况,根据表达情况分为MGMT阴性组和MGMT阳性组,并对患者长期随访,进行无进展生存时间和药物安全性的评定,对MGMT表达水平与替莫唑胺治疗效果行相关性分析。结果:15例患者肿瘤组织MGMT表达阴性者为8例(53.3%),MGMT表达阳性者为7例(46.7%);MGMT阴性组患者化疗6个疗程后,客观缓解率(ORR)为35.7%(3/8),明显高于MGMT阳性组的0(0/7);MGMT表达阳性组患者的中位无进展生存时间(mPFS)为6个月,而MGMT表达阴性组患者的mPFS目前无法得出,但明显长于MGMT阳性组,两组间差异具有统计学意义(P=0.000 2)。化疗不良反应均为2级以下的骨髓抑制和消化道反应。结论:基于替莫唑胺化疗方案的疗效与MGMT在肿瘤组织中的表达状态相关,MGMT表达与否可以用作胃肠胰神经内分泌瘤患者对替莫唑胺治疗反应的生物学指标。  相似文献   

6.
O6-甲基鸟嘌呤-DNA甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)是与恶性胶质瘤对替莫唑胺(temozolomide,TMZ)等烷化剂耐药相关的重要指标。本文总结根据MGMT表达状态选择不同的化疗方案,对复发恶性胶质瘤患者进行挽救性化疗的临床疗效。方法:经手术后病理确诊的复发恶性胶质瘤患者30例,均有可评价病灶。应用免疫组化法检测肿瘤MGMT表达状态,分为阳性组和阴性组。阳性组患者应用非TMZ常规5天方案或非烷化剂药物进行化疗,阴性组患者不限制化疗方案。结果:全组患者客观有效率为20%,中位无进展生存时间为8个月(95%CI:4.3~11.7),中位生存时间为16个月(95%CI:7.4~24.6)。其中MGMT阳性组16例,阴性组14例。阳性组和阴性组患者的客观有效率分别为18.8%和21.4%,中位无进展生存时间分别为7个月(95%CI:3.1~10.9)和8个月(95%CI:3.9~12.1),中位生存时间分别为16个月(95%CI:5.4~26.6)和16个月(95%CI:7.3~24.7),差异均无统计学意义(P>0.05)。结论:复发恶性胶质瘤挽救性化疗具有良好的临床获益,根据肿瘤MGMT表达进行个体化化疗,特别是对于MGMT阳性复发恶性胶质瘤患者,能够避免耐药,得到与MGMT阴性患者相当的临床疗效。   相似文献   

7.
MGMT在脑胶质瘤组织中的表达及其与患者生存期的关系   总被引:17,自引:0,他引:17  
Sun YH  Zhang YZ  Wang ZC  Sun MZ  Zhao DH 《癌症》2004,23(9):1052-1055
背景与目的:目前的研究已经证实DNA修复酶——6-氧-甲基鸟嘌呤DNA甲基转移酶(O6-methylguanine-DNAmethyltransferase,MGMT)在脑胶质瘤组织中的表达与肿瘤的耐药性有一定的关系,并且能够影响肿瘤的化疗效果。本研究通过分析MGMT在脑胶质瘤组织中的表达及其与患者生存期的关系,为基于耐药机制上的脑胶质瘤分子分类提供参考资料。方法:用组织芯片技术和免疫组织化学方法检测311例脑胶质瘤石蜡标本中MGMT的表达情况,并对所有患者进行手术后的5年随访。结果:MGMT表达阳性者126例,占40.51%(126/311)。其中,星形细胞瘤中阳性率为50.41%(61/121),少枝胶质细胞瘤中为25.71%(18/70),少枝星形细胞瘤中为28.13%(18/64),胶质母细胞瘤中为51.79%(29/56);在Ⅰ~Ⅱ级胶质瘤中,MGMT表达的阳性率为36.56%(68/186),而在Ⅲ~Ⅳ级胶质瘤中为46.40%(58/125),经χ2检验分析,两者之间有显著性差异(P<0.001);将MGMT的表达与患者生存期的关系绘制成Kaplan-Meier生存曲线,并进行log-rank分析,MGMT表达阳性者与阴性者之间的差异有显著性(P<0.05)。结论:MGMT在脑胶质瘤的异常表达与肿瘤的组织类型、病理级别有关,MGMT表达阳性患者的生存期明显低于表达阴性的患者。  相似文献   

8.
目的:探讨分子标志物在高级别胶质瘤患者预后评估中的价值。方法:收集2010年09月至2015年07月之间经我院收治的高级别胶质瘤患者31例,免疫组织化学染色检测患者肿瘤组织中Ki-67、6-氧-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、表皮生长因子受体(EGFR)、p53和基质金属蛋白酶-9(MMP-9)的表达;电话及门诊随访患者生存状况,分析上述分子标志物在高级别胶质瘤患者预后评估中的价值。结果:Ki-67和MGMT高表达患者的PFS明显低于低表达患者(P<0.05),但MMP-9、EGFR和p53表达水平与PFS间未见明显相关性(P>0.05)。多因素分析发现Ki-67是影响PFS的独立预后因素(RR=5.19,P<0.05)。结论:Ki-67是影响高级别胶质瘤患者PFS的独立危险因素,在预后评估中可能具有潜在的应用价值。  相似文献   

9.
目的探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)在恶性脑胶质瘤组织中的表达及其与预后的关系。方法选取2011年1月至2016年1月间中山市陈星海医院收治的经手术切除的64例恶性脑胶质瘤(Ⅲ、Ⅳ级)患者,采用免疫组化法检测肿瘤组织中MGMT蛋白的表达,评定治疗效果,追踪生存时间(OS),评价MGMT与生存时间之间的关系。结果 MGMT阳性表达率为62.5%,MGMT阴性表达率为37.5%。WHOⅢ级恶性胶质瘤组织中MGMT阳性表达率与Ⅳ级比较,差异无统计学意义(P>0.05);但Ⅳ级恶性胶质瘤MGMT(++)表达率为60.0%,明显高于Ⅲ级的48.3%,差异有统计学意义(P<0.05)。MGMT阴性患者总有效率(ORR)为62.5%,高于阳性患者的17.5%;与MGMT(-)比较,MGMT(+)和MGMT(++)平均OS均降低,差异均有统计学意义(均P<0.05)。MGMT阳性患者最长无进展生存时间(PFS)为32个月,MGMT(-)最长PFS为40个月。结论 MGMT表达与脑胶质瘤恶性程度有关,表达强度越高,恶性程度越高,检测MGMT可一定程度预知脑胶质瘤治疗的有效率及预后。  相似文献   

10.
目的:探讨弥漫大B细胞淋巴瘤(DLBCL)中微血管密度、Ki-67标记指数、bcl-6阳性率与患者预后的关系.方法:应用免疫组织化学染色法检测血管内皮细胞特异性标记物CD34和Ki-67、bcl-6的表达,通过形态学计量法计数肿瘤内微血管密度.结果:1)肿瘤微血管密度与Ki-67标记指数有关(P<0.01),与bcl-6表达阳性率无关;2)Kaplan-Meier分析显示微血管计数≤21.5(×200倍)的弥漫大B细胞淋巴瘤预后较好,而微血管计数>21.5(×200倍)预后较差:3)肿瘤细胞Ki-67的标记指数值在28.2%~85.6%之间,中位数59.4%,标记指数>59.4%较≤59.4%者预后差:4)bcl-6表达阳性率在12.4%~90.8%之间,中位数42.0%,阳性率>42.0%较≤42.0%者预后好.结论:弥漫大B细胞淋巴瘤微血管密度计量、Ki-67标记指数和bcl-6阳性率是评价患者预后的重要指标.  相似文献   

11.
Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studies.  相似文献   

12.
The need for more accurate prediction of the biological behavior of brain tumors has lead to the use of immunohistochemical methods for assessment of proliferating cell nuclear antigens such as Ki-67. There is a variable association of glioma Ki-67 labeling index with patient survival. Brain invasion by individual tumor cells also defines biological aggressiveness, and can be assessed in vitro. Further, proliferation and migration seem to be mutually exclusive behaviors for a given cell at a point in time. We studied the relationship between Ki-67 labeling index and invasion rate in a group of 10 gliomas, and 2 meningiomas. Human tumor spheroids obtained from operative speciments were co-cultured with fetal rat brain aggregates, and invasion rate was measured by confocal microscopic observation. There was no correlation between two measures of invasion and Ki-67 labeling. This finding supports the dichotomous nature of glioma proliferation and invasion, and may in part explain the limited usefulness of proliferation marker labeling.  相似文献   

13.
BACKGROUND: To estimate the effectiveness of expression of the tumor proliferative marker Ki-67 antigen (Ki-67) as a postoperative prognostic marker, the authors analyzed Ki-67 expression and its correlation with postoperative survival and other clinicopathologic factors, including preoperative smoking habits, in patients with resected nonsmall cell lung carcinoma (NSCLC). METHODS: A total of 156 patients with resected NSCLC at the study institution were investigated. Postoperative survival rates were estimated based on demographic and clinicopathologic factors, including Ki-67 expression and preoperative tobacco smoking habits. RESULTS: The overall postoperative 5-year survival rate in patients with high Ki-67 labeling indices (>/= 20%) was 39.6% compared with 67.7% in patients with low Ki-67 labeling indices. This finding was significant for all resected cases and for each pathologic disease stage (P < 0.05). The postoperative 5-year survival rate in patients with a history of heavy smoking (>/= 30 pack-years) was 47.6% compared with 62.5% for other patients (P = 0.027). This result was especially significant in patients with International Union Against Cancer Stage I disease and in patients with nonsquamous cell carcinoma (P < 0.03). The authors also observed a positive correlation between the Ki-67 labeling index and preoperative smoking habits (P = 0.0002). Multivariate analysis demonstrated that lymph node involvement, tumor differentiation, and Ki-67 labeling index were significant prognostic factors in NSCLC (P < 0.01). CONCLUSIONS: Tumor Ki-67 expression is a strong prognostic factor in NSCLC, especially adenocarcinoma. It may be hypothesized that tobacco mutagenicity may play a role in the growth and extension of NSCLC, which is one of the major impediments to postoperative survival in patients with a history of heavy smoking.  相似文献   

14.
Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that mostly occurs in early childhood and has poor prognosis despite aggressive therapy. Adult cases are rare and, as far as we are aware, only 30 cases have been reported to date. Here we present the case of a 27-year-old female with left parietal AT/RT with the chief complaint of numbness of the right superior limb. First, the tumor was surgically removed and the diagnosis was grade II glioma. With additional radiotherapy, the clinical course after surgery was favorable. After 6 years, she had an operation for recurrence and the diagnosis was grade III glioma. Temozolomide was prescribed, and a disease-free period of 2 years followed. Surgery was performed for a third time for second recurrence with histology of diffuse growth of rhabdoid cells. Immunohistochemistry was partially positive for vimentin and epithelial membrane antigen. Ki-67 labeling index was extremely high and tumor cells showed no staining of INI1 suggestive of diagnosis of AT/RT. We re-evaluated past specimens and none had immunoreactivity of INI1. Ki-67 labeling index and O-6 methylguanine DNA methyltransferase (MGMT) staining were also re-examined and both increased gradually. She is still alive without recurrence for more than 1 year. As far as we are aware, this is the second longest survival of an adult with AT/RT.  相似文献   

15.

Objective  

This phase II study aimed at investigating the correlation between O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and protein expression, together with Ki-67 labeling index (LI), to response, time to progression (TTP), and overall survival (OS) in newly diagnosed glioblastoma multiforme (GBM) patients treated with temozolomide (TMZ) concomitant with and adjuvant to radiotherapy (RT).  相似文献   

16.
The growth fractions in endoscopically biopsied materials from 121 patients with gastric carcinomas were determined by immunohistochemical staining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings and clinical outcome. The Ki-67 labeling rates ranged from 4.6 to 52% (mean: 22%). A significant correlation was found between Ki-67 labeling rates of biopsied materials and those of resected specimens. The tumors showing Ki-67 labeling rates of greater than 22% are more likely to have lymph node metastasis, lymphatic invasion of serosal invasion than those with the rates below 22%. In addition, Ki-67 labeling rates were closely associated with prognosis. Tumors with high Ki-67 labeling rates (greater than 22%) were related to poor prognosis, whereas those with low Ki-67 labeling rates were associated with favorable prognosis. The immunohistochemical staining of proliferating cells in endoscopically biopsied specimens of gastric carcinomas using the Ki-67 monoclonal antibody may be useful in assessing prognosis in carcinoma of the stomach.  相似文献   

17.
The purpose of this study was to investigate the therapeutic effect of intracarotid infusion of 20% mannitol with ACNU chemotherapy in Fischer 344 rats with intracerebrally implanted 9L gliosarcoma, compared with giving them only ACNU intraperitoneally. Thirty 9L gliosarcoma bearing Fischer 344 rats were evaluated in the following 3 groups. Group I: control (no treatment); group II: treated by ACNU 20 mg/kg intraperitoneally on the 7th day after implantation of 9L gliosarcoma cells; group III: treated by intracarotid infusion of 20% mannitol 3.1 ml/min. and with the same dose of ACNU as in group II. Mean survival time after the inoculation of tumor cells into the brain was 15.1 days (group I), 21.8 days (group II) and 27.9 days (group III). In group II all tumor-bearing Fischer rats died within 24 days after inoculation of tumor cells, whereas in group III 5 out of 6 rats survived more than 25 days after them. Group III evidenced necrosis and degenerative findings with vacuole and microcyst without vascular proliferation in tumor tissues more than group II on the 7th day after ACNU treatment for the experimental brain tumor. On the 7th day after ACNU treatment of each group, BrdU labeling index was calculated in order to evaluate tumor proliferation. The Mean BrdU labeling index in tumor cells of group III demonstrated 7.5%, against 14.5% (about one half) in group II. From our experimental study of survival time and BrdU labeling index, it is suggested that osmotic blood brain barrier disruption chemotherapy by intracarotid infusion of 20% mannitol and ACNU was more effective than simple treatment by intraperitoneal injection of ACNU in the Fischer rats with intracerebrally implanted 9L gliosarcoma.  相似文献   

18.
Cell proliferation was assessed in 33 invasive breast carcinomas by an immunoperoxidase procedure using the monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The antibody labeled a variable proportion of tumor cells ranging from 3% to 60%. High numbers of Ki-67-positive cells were found in tumors with high mitotic rates, high nuclear grade, high histologic grade, and in premenopausal women. Tumors with low and intermediate Ki-67 labeling rates often had high estrogen receptor content, whereas tumors with high Ki-67 labeling rates were usually estrogen receptor negative. These correlations are similar to those previously reported for other measurements of cell cycle kinetics such as thymidine labeling index and suggest that immunohistochemical staining of invasive breast carcinoma for the Ki-67 epitope may provide cell cycle information not otherwise readily available to the clinician and may be useful in assessing prognosis in carcinoma of the breast.  相似文献   

19.
目的:研究弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)对化疗不敏感和复发现象是否与凋亡抑制因子survivin、bcl-2蛋白及增殖因子ki-67蛋白的表达有关。方法:收集2000-2003年本院收治的经病理学证实的DLBCL患者,符合入组条件41例,分析IPI各因素及疗效与预后之间的相关性。同时,20例可获取病理组织标本的患者,用免疫组化方法进行survivin、bcl-2及ki-67蛋白表达的测定,并对其进行预后相关性分析。结果:单因素分析显示临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平及疗效均为DLBCL的独立预后因素,是否合并放疗或使用美罗华对预后影响无统计学差别;多因素分析提示ECOG评分与疗效是影响无进展生存的独立预后因素。免疫组化分析显示ki-67乘积高的患者生存期较短(P<0.05),复发组的平均ki-67指数及bcl-2乘积较未复发组高(前者P<0.05,后者P=0.069),bcl-2乘积高的患者死亡率较高(P<0.05),survivin核阳性患者较核阴性患者生存期短,但差异未达到统计学意义(P>0.05)。结论:临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平、疗效及ki-67均为DLBCL的独立预后因素,Ki-67指数高为复发危险因素,bcl-一2乘积高为预后危险因素,survivin核阳性可能是预后不良因素。  相似文献   

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