基质金属蛋白酶-2在妊娠滋养细胞疾病中的表达及意义

目的:探讨基质金属蛋白酶-2(m atrix m etalloprote inase,MMP-2)在妊娠滋养细胞疾病中的表达。方法:应用免疫组化SP法检测正常早孕妇女胎盘绒毛10例、葡萄胎20例、侵蚀性葡萄胎32例及绒毛膜癌16例组织中MMP-2的表达情况。结果:MMP-2主要表达于合体滋养细胞、绒毛外滋养细胞。正常早孕绒毛组织、妊娠滋养细胞疾病组织中,MMP-2均有阳性表达,早孕绒毛与早孕期葡萄胎间有显著差异(P<0.05),与葡萄胎病理分型、胎次无相关性,早孕期葡萄胎MMP-2阳性表达率显著高于晚孕期葡萄胎(P<0.05)。正常绒毛组MMP-2阳性表达率与葡萄胎组、侵蚀性葡萄胎组和绒毛膜癌组相比有显著性差异(P<0.05)且有逐渐上升趋势,但其余各组间无统计学意义。MMP-2表达与侵蚀性葡萄胎、绒毛膜癌临床分期无相关性。侵蚀性葡萄胎组中未化疗者MMP-2阳性表达率显著高于化疗者(P<0.05);绒毛膜癌组中未化疗组MMP-2阳性表达率高于化疗组,但无统计学意义。结论:MMP-2与滋养细胞的浸润活性呈正相关,与孕周呈负相关,可能与正常滋养细胞浸润行为的时空阶段性和限制性有关。随着妊娠滋养细胞疾病恶性程度升高MMP-2逐渐呈强表达,化疗后其阳性表达明显下降,提示MMP-2可能作为临床早期诊断妊娠滋养细胞疾病、判断治疗疗效及预后的重要指标之一。     

E-cadherin及nm23-H1在滋养细胞疾病中的表达及意义

目的:探讨E-cadherin及nm23-H1基因在妊娠滋养细胞疾病发生发展中的作用.方法:采用免疫组化法检测24例葡萄胎(随访2年以上未发生恶变)、15例侵蚀性葡萄胎、15例绒毛膜上皮癌、18例正常绒毛组织的石蜡包埋标本E-cadherin和nm23-H1基因的表达状况.结果:E-cadherin的表达在正常早孕绒毛高于侵蚀性葡萄胎和绒毛膜癌(P＜0.01),葡萄胎高于侵蚀性葡萄胎和绒毛膜癌(P＜0.05).nm23-H1的表达正常早孕绒毛明显高于恶性滋养细胞疾病(P＜0.01),葡萄胎高于侵蚀性葡萄胎(P＜0.01)和绒毛膜癌(P＜0.05).在葡萄胎和恶性滋养细胞疾病中E-cadherin和nm23-H1基因的表达均为正相关.结论:滋养细胞疾病E-cadherin和nm23-H1表达与其侵袭性相关,二者可能成为葡萄胎预后的标志物.在侵袭转移过程中细胞滋养细胞较合体滋养细胞更为重要.     

妊娠滋养细胞肿瘤nm23H1和PCNA的表达及其临床意义

目的 观察ｎｍ２３Ｈ１表达与妊娠滋养细胞肿瘤转移及细胞地殖状态的关系，并观察化疗对滋养细胞肿瘤细胞增殖状态的影响。方法 采用免疫组化方法检测４８例妊娠滋养细胞肿瘤手术标本、１０全恶性循环葡萄胎和１０例正常早孕绒毛组织刮宫标本中ｎｍ２３Ｈ１和ＰＣＮＡ的表达。结果 正常早孕绒毛或葡萄胎的ｎｍ２３Ｈ１，表达较妊娠滋养细胞肿瘤强（Ｐ〈０．０１），妊娠滋养细胞肿瘤中侵蚀性葡萄胎较绒癌强（Ｐ，０．０５），ＷＯ     

滋养细胞疾病中p27蛋白表达的研究

目的 探讨周期素依赖激酶抑制剂ｐ２７蛋白在滋养细胞中的表达及其与滋养细胞疾病发生、发展和预后的关系。方法 采用免疫组织化学ＳＰ（ＬＳＡＢ）法检测３５例滋养细胞中ｐ２７蛋白的表达情况。结果 ｐ２７蛋白在１０例正常早孕绒毛和１５例良性葡萄胎中的表达阳性率明显高于１１例侵蚀性葡萄胎和９例绒毛膜癌（Ｐ〈０．０５）。正常早孕绒毛和良性葡萄胎ｐ２７蛋白表达阳性率分别为８０．０％（８／１０）和７３．３％（１１／     

VE—cadherin在妊娠滋养细胞疾病的表达及其临床意义初步探讨

目的：探讨VE—cadherin在妊娠滋养细胞疾病的表达及其临床价值。方法：采用逆转录聚合酶链反应技术,检测22例正常早孕绒毛和非恶变葡萄胎23例,恶变葡萄胎12例,侵蚀性葡萄胎11例和绒毛膜癌9例共55例妊娠滋养细胞疾病组织中VE—cadherinmRNA的表达量。结果：VE—cadherinmRNA在正常早孕绒毛与非恶变葡萄胎组织的表达量的差异无统计学意义（P〉0．05）;恶变葡萄胎、侵蚀性葡萄胎和绒癌的表达量明显低于正常早孕绒毛和非恶变葡萄胎;侵蚀性葡萄胎和绒癌的表达量低于恶变葡萄胎;绒癌的表达量低于侵蚀性葡萄胎（P〈0．01）。结论：VE—cadherinmRNA的表达下调可能是滋养细胞恶性转化的早期事件,与葡萄胎的恶变有关。检测VE—cadherin的表达可望成为预测葡萄胎恶变以及妊娠滋养细胞肿瘤（GTT）预后评价的参考指标。     

部分性葡萄胎临床特点探讨

妊娠滋养细胞疾病中的葡萄胎，根据病理及细胞遗传学性质可分为完全性葡萄胎（complete hydatidiform mole，CHM）和部分性葡萄胎（paaial hydatidiform mole，PHM）两种。CHM为没有胚胎的异常妊娠，胎盘绒毛全部变成大小不等的水泡状物，滋养层细胞增生，血管消失，而PHM胎盘绒毛部分变化，部分绒毛水肿可见绒毛正常形态，有的可见胎儿及胎儿附属物，一些滋养细胞增生，病变局限。从细胞遗传学区分PHM90％以上核型为三倍体，其中23条染色体为母源性，另46条染色体为父源性，导致69xxx或69xxy的核型；CHM为二倍体，染色体均为父源性，由于空卵单精子受精，     

葡萄胎和绒毛膜癌基因表达谱改变与滋养细胞增生的关系

目的研究葡萄胎和绒毛膜癌(绒癌)基因表达谱改变与滋养细胞增生的关系。方法用含4096条基因的表达谱芯片,对2例完全性葡萄胎、2例正常绒毛及原代培养的早孕绒毛滋养细胞和绒癌JAR细胞株滋养细胞进行基因差异表达谱分析。用免疫组化、免疫印迹和反转录聚合酶链反应(RT-PCR)方法,对正常绒毛和葡萄胎组织及绒癌JAR和JED3细胞中与DNA合成有关的一些酶表达水平进行印证。结果2例葡萄胎标本中,均有显著差异表达基因89条,占基因总数的2．2％。葡萄胎与正常绒毛相比,24条基因表达显著增高(上凋),65条基因显著降低(下调)。JAR细胞与正常原代培养滋养细胞相比,432条基因下调,380条基因上调。葡萄胎和绒癌细胞中,共同下调基因有46条,共同上调基因有13条。在葡萄胎和绒癌中,抑制细胞生长的基因下调,而与细胞增生、恶性转化、转移及耐药等有关的基因上调。经免疫组化、免疫印迹和RT-PCR方法证实,在葡萄胎、绒癌JAR和JED3细胞中,与DNA合成有关的胸腺嘧啶核苷激酶1和核苷酸还原酶小亚基的表达显著增高。结论葡萄胎和绒癌存在着异常表达基因,滋养细胞增生可能与DNA合成酶异常高表达有关。     

p21在妊娠滋养细胞疾病中的表达及临床意义

目的探讨p21在妊娠滋养细胞疾病（GTD）中的表达及其在疾病发生、发展中的作用。方法：用免疫组化SP法对10例早孕（6～12周）人工流产绒毛，40例葡萄胎，10例侵蚀性葡萄胎发6例绒毛膜癌组织进行了p21蛋白测定。结果：p21在4种不同组织中的阳性表达中分别为70％、75％、100％、100％；p21在葡萄胎和早孕绒毛之间表达无差异（P＞0．05），而在侵蚀性葡萄胎、绒毛膜癌与早孕绒毛之间存在差异（均为P＜0．05）。葡萄胎组织中，p21染色强度与组织分级无相关性（均为P＞0．05）；p21染色在良性葡萄胎中比以后恶变的葡萄胎中表达高，存在差异（P＜0．05）。结论（Ⅰ）p21与GTD的发展呈正相关，在妊娠滋养细胞肿瘤（GTT）中可能存在Ras基因突变，突变后的Rasp21表达增加，降解减慢，持续传递细胞增殖信息，有促进细胞增殖的效应；（2）在葡萄胎组织中，p21高表达的病人预后良好，因而p21对判断葡萄胎的预后可能具有一定意义。     

VE-cadherin在妊娠滋养细胞疾病的表达及其临床意义初步探讨

目的:探讨VE-cadherin在妊娠滋养细胞疾病的表达及其临床价值.方法:采用逆转录聚合酶链反应技术,检测22例正常早孕绒毛和非恶变葡萄胎23例,恶变葡萄胎12例,侵蚀性葡萄胎11例和绒毛膜癌9例共55例妊娠滋养细胞疾病组织中VE-cadherin mRNA的表达量.结果:VE-cadherin mRNA在正常早孕绒毛与非恶变葡萄胎组织的表达量的差异无统计学意义(P＞0.05);恶变葡萄胎、侵蚀性葡萄胎和绒癌的表达量明显低于正常早孕绒毛和非恶变葡萄胎;侵蚀性葡萄胎和绒癌的表达量低于恶变葡萄胎;绒癌的表达量低于侵蚀性葡萄胎(P＜0.01).结论:VE-cadherin mRNA的表达下调可能是滋养细胞恶性转化的早期事件,与葡萄胎的恶变有关.检测VE-cadherin的表达可望成为预测葡萄胎恶变以及妊娠滋养细胞肿瘤(GTT)预后评价的参考指标.     

P21在妊娠滋养细胞疾病中的表达及临床意义

目的，探讨P21在妊娠滋养细胞疾病（GTD）中的表达及其在疾病发生，发展中的作用。方法：用免疫组化SP法对10早孕（6－12周）人工流产绒毛，40例葡萄胎，10例侵蚀性葡萄胎及6例绒毛膜癌组织进行了P21蛋白测定，结果：P21在4种不同组织中的阳性表达率分别为70％、75％、100％、；P21在葡萄胎和早孕绒毛之间表达无差异（P＞0．05）。而在侵蚀性葡萄胎、绒毛膜癌与早孕绒毛之间存在差异（均为P＜0．05）。葡萄胎组织中，P21染色强度与组织分级无相关性（均为P＞0．05）；P21染色在良性葡萄胎中比以后恶变的葡萄胎中表达高，存在差异（P＜0．05）。结论（1）P21与GTD的发展呈正相关；在妊娠养细胞肿瘤（GTT）中可能存在Ras基因突变，突变后的Rasp21表达增加，降解减慢；持续传递细胞增殖信息，有促进细胞增殖的效应；（2）在葡萄胎组织中，P21高表达的病人预后良好，因而21对判断葡萄胎的预后可能具有一定意义。     

MGMT和Ki-67在胶质母细胞瘤中的表达对ACNU化疗预后的影响

背景与目的:胶质母细胞瘤是预后极差的常见颅内恶性肿瘤,手术切除、放疗和化疗联合应用是常规治疗方法;Ki-67是肿瘤细胞生长活跃程度的标志,与胶质瘤的分级显著相关;O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)是一种DNA修复蛋白,其表达影响肿瘤对化疗药的敏感性。本研究通过免疫组织化学方法对胶质母细胞瘤的Ki-67和MGMT进行检测,探讨其对胶质母细胞瘤化疗预后的影响。方法:总结39例脑胶质母细胞瘤患者的性别、年龄、术前Karnofsky评分、生存时间等;将患者手术切除标本石蜡切片进行Ki-67和MGMT的免疫组织化学染色,计算细胞核染色阳性率;多元逐步回归分析法判断Ki-67和MGMT的表达与患者生存时间的关系。结果:本组病例男22例,女17例;年龄21～75岁,平均54.0岁;生存时间6～38个月,平均19.3个月,中位生存期17.0个月。Ki-67在所有标本有不同程度的表达,表现为胞核明显染色,Ki-67阳性率4.0%～26.6%,平均10.5%。MGMT除2例外均有不同程度表达,胞浆染色较淡,胞核可见浓染,MGMT胞核阳性率0%～51.4%,平均21.2%。Ki-67阳性率与生存时间无相关性。MGMT胞核阳性率与生存时间呈负相关(P=0.002)。结论:Ki-67在胶质母细胞瘤表达与肿瘤的预后无关。MGMT在胶质母细胞瘤表达与肿瘤化疗后的预后有关,MGMT的检测对胶质母细胞瘤术后化疗可能有指导意义。     

滋养层细胞肿瘤的凝集素组化研究

运用ABC和PAP法研究了正常绒毛、胎盘绒毛水泡状变性(水肿绒毛)、非侵袭性葡萄胎、侵袭性葡萄胎和绒毛膜上皮癌与刀豆素、麦胚素等5种凝集素的结合特点。刀豆素与合体滋养层和细胞滋养层细胞胞浆成分结合,其染色强度大致随滋养层细胞增生程度的升高而增强,以绒癌为甚;麦胚素与绒癌、侵袭性或非侵袭性葡萄胎细胞滋养层细胞膜的结合则较正常绒毛或水肿绒毛为弱。因此,刀豆素和麦胚素组化结合反应不仅可直观了解滋养层细胞及其良恶性肿瘤细胞结构糖成分的微细变化,也可用于判断滋养层细胞增生程度,为区别不同性质的滋养层细胞疾病,提供新的参考指标。     

Ki-67 immunostaining and other prognostic factors including tobacco smoking in patients with resected nonsmall cell lung carcinoma

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.     

Cyclooxygenase-2 expression and its relationship with proliferation of colorectal adenomas

BACKGROUND: Cyclooxygenase (COX)-2 may be linked to carcinogenesis. In the previous study, we examined COX-2 expression immunohistochemically in 95 adenomas and reported a significant correlation between its expression and the grade of dysplasia. To clarify the correlation between COX-2 expression and cell proliferation, we investigated Ki-67 labeling index using immunohistochemistry and its correlation with COX-2 expression. METHODS: Immunohistological staining for Ki-67 antigen was performed on 95 colorectal adenomas previously reported. RESULTS: The Ki-67 labeling index was significantly higher in the high-COX-2 group than in the low-COX-2 and negative groups in adenomas with moderate (44.5 +/- 6.4% vs 33.0 +/- 2.6%, 39.0 +/- 6.2%; P = 0.01, P < 0.001, respectively) or severe dysplasia (47.2 +/- 7.6% vs 40.3 +/- 7.2%, 35.0 +/- 5.4%; P = 0.02, P = 0.005, respectively). There was no correlation between Ki-67 labeling index and COX-2 expression in mild dysplasia. CONCLUSIONS: These results suggest that COX-2 may play a causal role in cell proliferation in carcinogenesis.     

Ki-67反义寡核苷酸抑制人肝癌细胞株HEPG-7402生长的体外试验

目的通过观察硫代磷酸化修饰的Ki-67抗原反义寡核苷酸(antisenseoligodeoxyribonucleoti-de,ASODN)抑制Ki-67抗原表达,从而抑制HEPG-7402细胞体外增殖,为今后肝癌的基因治疗提供新的手段。方法将Ki-67反义寡核苷酸(ASODN)作用于HEPG-7402细胞,MTT比色法测细胞增殖活性;免疫细胞化学(ImmunocellulerchemistryICC)方法检测Ki-67标记指数(LabelingindexLI)、RT-PCR方法观察Ki-67mRNA水平的改变。结果Ki-67ASODN作用组HEPG-7402细胞增殖受到明显抑制;Ki-67标记指数(LI)下降,Ki-67mRNA合成减少。结论针对Ki-67的反义寡核苷酸能抑制人肝癌细胞株的体外生长。     

Association between Ki-67 Labeling index and Histopathological Grading of Glioma in Indonesian Population

Background: Gliomas are the most frequent primary brain tumors. According to World Health Organization guidelines, gliomas are graded into four groups (Group I-IV). This histological grading will determine prognosis and treatment of the patient. Morphological criteria are not always accurate. Tumor proliferation index is a potent quantitative marker for tumor behavior and prognosis, also it’s the basis of gliomagenesis. Ki-67 immunohistochemistry examination for determining proliferation index has been suggested as an ancillary marker in deciding the definitive grading of glioma. Objective: To analyze the correlation between Ki-67 labeling index and histopathological grading of glioma in Indonesian population. Methods: One hundred and six formalin fixed-paraffin embedded tissue of glioma patients were collected from 4 different hospitals. Expression of Ki-67 was detected using immunohistochemistry staining and the labeling index was counted. The association between Ki-67 labeling index and histopathological grading was analyzed. Results: Age range of patient were 1-73-years old, with male predominance (55.70%). Glioblastoma was the most common diagnosis accounting for 41.51% of all samples. Ki-67 labeling index cut point of 6.35% was obtained and significantly sensitive and specific for determining low- or high-grade glioma (p<0.001). Conclusion: A significant association between Ki-67 labeling index and histopathological grading in Indonesian glioma patients has been revealed. The result of this study may be used to improve diagnostic and grading accuracy of glioma cases in Indonesia, especially in small biopsy specimens.     

Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer

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.     

Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors

The relationship between labeling indices of Ki-67 reactive antigen expressed by cycling cells and BrdUrd incorporated into S-phase cells was investigated in 20 patients with malignant tumors. Both of the labeling indices varied greatly from patient to patient; the labeling index of Ki-67 ranged from 37.5% to 1.9% with an average value of 16%, and the BrdUrd labeling index ranged from 23.4% to 1.6% with an average of 9.3%. The Ki-67 labeling index was higher than the BrdUrd labeling index. In general, the values of the Ki-67 labeling index were parallel to those of the BrdUrd labeling index, and the relation Y = 1.59X + 1.15 (r = 0.89) was obtained. In human solid tumors, therefore, the growth fraction can be easily estimated from the S-phase fraction size, and vice versa.