GFAP、Vim、MDR-1与EGFR在颅内星形细胞肿瘤中的表达及意义

目的探讨颅内星形细胞肿瘤的GFAP、Vim和MDR-1、EGFR的表达及意义.方法采用S-P法对101例颅内星形细胞肿瘤进行GFAP、Vim、和MDR-1、EGFR免疫组化标记,并对临床和病理资料及免疫组化结果进行统计分析.结果免疫组化标记能帮助区别星形细胞肿瘤的组织类型和分化程度.间变性星形细胞瘤和胶质母细胞瘤GFAP表达减弱,而Vim、MDR-1、EGFR的表达增强,恶性程度增加,术后生存率低(P＜0.005).结论免疫组化标记对星形细胞肿瘤术后化疗方案的制定及预后估计具有重要意义.间变性和肥胖细胞性星形细胞瘤更具恶性,易复发.胶质母细胞瘤恶性程度最高,预后差.     

bcl—2／JH融合基因在星形胶质细胞瘤中的表达及意义

目的通过bcl-2检测寻找判断星形胶质细胞瘤预后的一个重要参考指标.方法应用聚合酶链反应技术和免疫组化方法检测bcl-2/JH融合基因及其蛋白产物在34例星形胶质细胞瘤中的表达.结果根据Kernohn分级标准将Ⅰ、Ⅱ级星形胶质细胞瘤分为第一组19例,Ⅲ、Ⅳ级为第二组15例.结果显示第一组bcl-2/JH融合基因表达率57.9%(11/19),第二组6.7%(1/15),经统计学分析,P＜0.005.免疫组化检测bcl-2蛋白,第一组12例(63.2%)表达bcl-2蛋白,第二组9例(60.0%),经统计学分析P＜0.01.结论星形胶质细胞瘤的发生及其恶性程度与bcl-2/Ⅲ融合基因及其蛋白的表达有关.     

P21-ras、P53、Ki-67蛋白的表达与星形细胞瘤分化及预后的相关性研究

目的分析Ｐ２１－ｒａｓ、Ｐ５３、Ｋｉ－６７在星形细胞肿瘤中的表达,与肿瘤增生活性、分化和预后的关系。方法应用免疫组化ＬＳＡＢ法对６６例星形细胞瘤Ｐ２１－ｒａｓ、Ｐ５３、Ｋｉ－６７表达进行检测,对其中４７例有随访资料的肿瘤患者存活因素进行分析。结果Ｐ５３、Ｋｉ－６７的表达与肿瘤分级密切相关（Ｐ＜０．０１）。Ｐ５３、Ｋｉ－６７在肿瘤中的表达呈正相关（Ｐ＜０．０５）。Ｐ５３表达阳性,和Ｋｉ－６７表达指数高的肿瘤预后较差。Ｐ２１－ｒａｓ表达与肿瘤分化及预后未见显著差异。（Ｐ＞０．０５）。结论星形细胞瘤也存在Ｐ２１－ｒａｓ基因异常,Ｐ５３、Ｋｉ－６７能客观的反映肿瘤的增殖速度,分化和恶性程度,可以作为判断肿瘤预后的有用指标。     

p53、ras基因产物在胶质瘤中的表达与肿瘤分级的关系

目的以免疫组织化学方法探讨p53、ras基因产物在胶质瘤中的表达及其与肿瘤分级的关系.方法收集星形细胞瘤的病理检验蜡块共158例,作p53与p21蛋白的免疫组织化学检查.结果在158例星形细胞瘤中,p53和p21的阳性率分别为56.32%和51.9%,两者均可见于肿瘤的早期阶段.在从Ⅰ级～Ⅳ级的星形细胞瘤中,p53蛋白的阳性率依次上升,(P＜0.005),Ⅰ、Ⅱ级和Ⅲ、Ⅳ级的p53阳性率经t检验,(P＜0.05).说明在从良性星形细胞瘤到恶性星形细胞瘤的进展过程中,p53蛋白有对恶性星形细胞瘤有显著的标记作用.从Ⅰ级～Ⅳ级的星形细胞瘤中,p21蛋白的阳性率分别依次上升(P＜0.05).结论星形细胞瘤从良性或低恶性阶段向高度恶性的进展过程中.p53、ras癌基因产物的表达强度也随之增强.p53蛋白的过度表达与星形细胞瘤的恶性程度密切相关.     

《实用癌症杂志》2006年第21卷题录索引

基础研究、临床研究及经验交流颅脑DNA-PKcs、Bcl-2、Cyclin G在星形细胞瘤中的表达及与肿瘤分化和预后的关系………………………………………………………………………………………………康凯夫陈坚平黄金凤等2006,21(2):15250例脑胶质瘤三维适形放射治疗的疗效观察……………     

MDM2、P53蛋白在星形细胞瘤中的表达

目的　探讨 MDM2、p5 3蛋白在星形细胞瘤发病中的作用及其与肿瘤病理分级、预后的关系。方法　对确诊并有随访的 36例星形细胞瘤标本用免疫组化技术 SABC法进行 MDM2、p5 3蛋白定位观察。结果　发现 MDM2及 p5 3蛋白表达阳性率分别为 44 .4% (16 / 36例 )和 38.9% (14/ 36例 ) ,其阳性率与年龄、性别无关 ,但与肿瘤病理分级呈显著正相关 (分别为 P<0 .0 5 ,P<0 .0 1)。在 36例星形细胞瘤中MDM2和 p5 3共同阳性表达 9例 (2 5 % ) ,这 9例与单独MDM2蛋白或 p5 3蛋白阳性表达病例及 MDM2和 p5 3蛋白表达均阴性病例的一年和三年存活率有显著差别 (分别为P<0 .0 5 ,P<0 .0 1)。结论　 MDM2、p5 3蛋白阳性检出率有助于判断星形细胞瘤的恶性程度及预测肿瘤的预后     

BGA-A和MDM2及HSP70在星形细胞瘤中表达与肿瘤分化及预后的关系

目的:分析BGA-A、MDM2和HSP70在星形细胞瘤中的表达与肿瘤分化和预后的关系。方法:应用免疫组化SP法对54例脑原发性星形细胞瘤中BGA-A、MDM2和HSP70的表达进行观察,对其中41例取得随访资料的肿瘤患者存活因素进行分析。结果:BGA-A、MDM2和HSP70的表达与肿瘤分化和预后相关。MDM2在星形细胞瘤、间变型星形细胞瘤和多形性胶质母细胞瘤中差异有统计学意义,F=23·12,P0·01=5·61。BGA-A表达阳性和阴性的中位生存时间分别为23·5和16·5个月。MDM2和HSP70表达阳性中位生存时间分别为15·5和16·2个月,表达阴性中位生存时间分别为25·6和26·6个月。结论:BGA-A、MDM2和HSP70异常表达与星形细胞瘤分化和预后相关,可以作为判断肿瘤分化和预后的参考指标。     

脑星形细胞瘤中IL-6mRNA的表达研究

目的　研究IL 6mRNA在星形细胞瘤中的表达及其与星形细胞瘤病理分级的关系。方法　采用地高辛标记IL 6cDNA探针 ,运用原位杂交技术检测IL 6mRNA在 3 1例星形细胞瘤和 10例正常脑组织中表达。结果　星形细胞瘤低分化组、高分化组表达率均高于对照组 ,有显著性差异 ,分别为P <0 .0 1及P <0 .0 5。星形细胞瘤低分化组表达率大于高分化组 ,P <0 .0 5。表明IL 6mRNA表达率与组织类型及星形细胞瘤的分化程度有关。结论　IL 6可能参与星形细胞瘤的发生、发展过程 ,高分化的星形细胞瘤向恶性转化可能与IL 6mRNA过度表达有关系。     

脑星形胶质细胞瘤增殖与分化

 本文应用免疫组化方法在40例呈形胶质细胞瘤中研究PCNA和GFAP两种标记表达，原位观察与比较瘤细胞的增殖与分化。结果表明脑星形胶质细胞瘤中PCNA与GFAP表达率均为100％，PCNA表达强度与肿瘤分级呈正相关（P＜0．05），GFAP表达强度与肿瘤分级呈负相关（P＜0．01）。提示PCNA与GFAP的表达对于判断脑星形胶质细胞瘤的增殖活性，分化程度及判断肿瘤的恶性程度有一定的价值。     

NSCLC中DNA—PKcs的表达及其与凋亡相关蛋白关系的研究

目的检测非小细胞肺癌(NSCLC)中DNA依赖蛋白激酶催化亚基(DNA-PKcs)的表达,探讨其与凋亡相关蛋白表达之间的关系.方法采用免疫组化SP法检测113例NSCLC患者肿瘤组织中DNA-PKcs、p53和bcl-2的表达.结果 NSCLC中DNA-PKcs、p53和bcl-2的检出率分别为89.38%、61.95%及59.29%;DNA-PKcs的表达顺序依次为细支气管肺泡癌>腺癌>腺鳞癌>鳞癌,而且DNA-PKcs表达水平随肿瘤分化程度的增高亦逐渐增高,差异均具有高度显著性(P<0.05),但其表达与淋巴结转移无明显关系;p53在不同临床病理类型NSCLC中的表达无明显差别;bcl-2在不同组织学类型NSCLC中的表达顺序依次为鳞癌>腺鳞癌>腺癌>细支气管肺泡癌,差异具有高度显著性(P<0.01),但其表达与肿瘤分化程度及淋巴结转移无关;DNA-PKcs与p53(P<0.01)、p53和bcl-2(P<0.05)的表达之间有显著相关性.结论 DNA-PKcs高表达导致的DNA损伤修复系统活性增高以及突变型p53和bcl-2过表达导致的凋亡抑制相互影响、共同作用,可能是形成NSCLC放疗抗拒性的重要因素.     

Expression of Cell Cycle-Related Proteins,p16, p53 and p63 as Important Prognostic Markers in Gallbladder Adenocarcinoma

Gallbladder cancer, the most common biliary tract malignancy, is a highly malignant neoplasm. In the present work, we have analyzed the significance of cell cycle-related proteins to predict prognosis and to provide guidance for optimal therapeutic decision-making in patients with gallbladder adenocarcinoma. The expressions of p16, p21, p27, p53, p63, cyclin D1, bcl-2 and bcl-6 were examined in a tissue microarray constructed from 96 cases of gallbladder adenocarcinoma by immunohistochemistry and correlated with clinicopathologic prognostic factors. Expression of p16 was correlated with a low pT stage, adenoma background and good prognosis. Cases with p63 expression showed a higher T stage, more frequent perineural invasion and poor prognosis when compared to cases without p63 expression. Over-expression of p53 or loss of p53 was associated with poor tumor differentiation, frequent distant metastasis and low disease-specific survival rate. The expressions of p21, p27, bcl-2, bcl-6 and cyclin D1 were not significant prognostic factors for gallbladder adenocarcinoma. These results indicate that p16, p63 and p53 can be used as prognostic markers in gallbladder adenocarcinoma; especially p53 and p63 as poor prognostic markers and p16 as a favorable prognostic marker.     

Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression

Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis.     

DNA-PKcs表达与乳腺癌临床病理特征关系的研究

目的:研究DNA依赖蛋白激酶催化亚单位(DNA-PKcs)表达与浸润性乳腺癌临床病理特征的关系。方法:应用组织芯片技术和免疫组织化学方法检测101例浸润性乳腺癌中DNA-PKcs以及ER、PR、c-erbB-2的表达情况,采用χ2检验及Spearman秩和相关检验分析结果。结果:DNA-PKcs表达与浸润性乳腺癌的肿瘤大小、淋巴结转移数量、TNM分期均呈负相关(分别为r=-0.319,P=0.001;r=-0.378,P=0.000;rs=-0.428,P=0.000);与ER表达呈正相关(rs=0.279,P=0.005);与患者年龄、肿瘤组织学分级、及PR、c-erbB-2表达的关系无统计学意义(P>0.05)。结论:DNA-PKcs低表达与浸润性乳腺癌的进展及淋巴结转移关系密切,有可能成为预测乳腺癌预后重要的生物学指标。     

Rsf-1在星形细胞瘤中的表达及其与临床病理因素的关系

目的:星形细胞瘤是中枢神经系统最常见的神经上皮性肿瘤,高级别的星形细胞瘤呈浸润性生长并且预后不良,重塑因子-1（Rsf-1）是位于人类染色体11q13.5 区域的RSF基因的表达产物,在多种恶性上皮性肿瘤中都有异常高表达的现象,并且与多种肿瘤的恶性进展及不良预后相关,本文旨在研究Rsf-1在星形细胞瘤中的表达及其与患者临床病理因素的关系。方法:选取2006年至2012年间星形细胞瘤术后石蜡标本130例,WHO组织学分级Ⅰ-Ⅳ级,通过免疫组织化学染色检测Rsf-1在星形细胞瘤中的表达水平。应用卡方检验统计Rsf-1的表达与患者临床病理因素的关系,Kaplan-Meier分析Rsf-1的表达与患者预后的关系。结果:Rsf-1在部分的星形细胞瘤中异常高表达（63/130）,并且其高表达与肿瘤大小、WHO分级及Ki-67指数呈正相关(P<0.01),而与年龄、性别和肿瘤的发生部位没有明显关系(P>0.05),Kaplan-Meier曲线表明Rsf-1的高表达与星形细胞瘤患者不良预后呈正相关(P<0.001)。结论:Rsf-1的在星形细胞瘤中异常高表达,并且与肿瘤大小、WHO分级、Ki-67指数及不良预后等关系密切,Rsf-1可能在星形细胞瘤的发生发展中发挥作用。     

Immunohistochemical Markers for Prognosis of Anaplastic Astrocytomas

Among the entire spectrum of astrocytic neoplasms, just anaplastic astrocytoma (or grade III astrocytoma) appears to be a more enigmatic tumor entity with vague criteria for pathological diagnosis, unclear biological behavior and diverse clinical outcome. Attempts have been made to identify biological markers that would be useful in prediction of prognosis of anaplastic astrocytomas but the results obtained are controversial. In the present study, survival data on 63 patients with anaplastic astrocytoma were studied to evaluate a possible association between clinical outcome and expression of some immunohistochemical variables. Both the progression-free (PFS) and overall (OS) survival times were significantly reduced for patients older than 45 years, for anaplastic astrocytomas containing multiple mitoses, for Ki-67 LI > 5%, for cyclin A LI > 4% and for PTEN-negative tumors. We found no differences in survival times in patients with or without p53 immunoreactivity and also in cases with different values of p16 and p27 immunostaining. Multivariate analysis revealed that risk of tumor progression and death is independently associated with tumors containing multiple mitoses and for PTEN-negative tumors. According to the data from the CART modeling, tumors were subdivided based on the three following subsets: (1) Anaplastic astrocytomas with solitary mitosis. (2) Anaplastic astrocytomas with multiple mitoses and PTEN positivity. (3) Anaplastic astrocytomas with multiple mitoses and PTEN negativity. Thus, the results obtained reveal the advantage of combined approach including evaluation of routine histological parameters and immunohistochemical variables for further clinical subdivision of anaplastic astrocytomas.     

DNA-PKcs表达与乳腺癌临床病理特征关系的研究

目的：研究DNA依赖蛋白激酶催化亚单位（DNA-PKcs）表达与浸润性乳腺癌临床病理特征的关系。方法：应用组织芯片技术和免疫组织化学方法检测101例浸润性乳腺癌中DNA-PKcs以及ER、PR、c-erbB-2的表达情况,采用χ2检验及Spearman秩和相关检验分析结果。结果：DNA-PKcs表达与浸润性乳腺癌的肿瘤大小、淋巴结转移数量、TNM分期均呈负相关（分别为r=-0.319,P=0.001;r=-0.378,P=0.000;rs=-0.428,P=0.000）;与ER表达呈正相关（rs=0.279,P=0.005）;与患者年龄、肿瘤组织学分级、及PR、c-erbB-2表达的关系无统计学意义（P〉0.05）。结论：DNA-PKcs低表达与浸润性乳腺癌的进展及淋巴结转移关系密切,有可能成为预测乳腺癌预后重要的生物学指标。     

Cdk9 regulates neural differentiation and its expression correlates with the differentiation grade of neuroblastoma and PNET tumors

Cdk9 is a member of the Cdc2-like family of kinases. Its cyclin partners are members of the family of cyclin T (T1, T2a and T2b) and cyclin K. The Cdk9/Cyclin T complex appears to be involved in regulating several physiological processes. Recently, Cdk9 has been identified as a regulator of the differentiation program of several cell types, such as muscle cells, monocytes and lymphocytes, suggesting that it may have a function in controlling specific differentiative pathways. We analyzed whether Cdk9 and Cyclin T1 may be involved in the regulation of neuron and astrocyte differentiation. Cdk9 and Cyclin T1 expression levels were monitored during the differentiation program of neuroblastoma and astrocytoma cell lines. Our results suggest that Cdk9/Cyclin T1 complex may be required for neuron differentiation induced by retinoic acid, because the expression level of the complex varies during differentiation, but no significant changes were observed in its expression in the astrocytoma cell line. In addition, the expression of Cdk9 and Cyclin T1 was evaluated by immunohistochemistry in samples of neuroblastoma, PNET (Primary Neuroectodermal Tumor) and astrocytoma tumors of different grades, in order to assess whether there was a correlation between Cdk9 expression and tumor grading. Our results show that in neuroblastoma and PNET tumor samples Cdk9 is more expressed the more differentiated the tumor is. Conversely, no significant alteration of Cdk9 expression was observed in astrocytoma tumor samples of different grades, thus confirming the results obtained for the cell lines.     

原发星形细胞瘤中TP53、PDGF、EGFR的表达及与临床病理特征和预后的相关性

目的 探讨TP53、PDGF、EGFR在原发星形细胞瘤中的表达,分析其与临床病理特征和预后的相关性.方法 回顾性收集90例原发星形细胞瘤患者临床病理资料,采用免疫组织化学检测原发星形细胞瘤组织样本中TP53、PDGF、EGFR表达,随访患者生存情况,Cox回归分析影响预后的因素.结果 TP53表达于细胞核,PDGF、E...     

脑星形细胞瘤中TIP30、VEGF和CD34的表达及其相关性研究

目的探讨脑星形细胞瘤中TIP30、血管内皮生长因子（VEGF）、CD34的表达情况及其病理意义。方法采用免疫组织化学Elivision plus两步法,检测19例正常脑组织及71例星形细胞瘤组织中TIP30、VEGF及CD34的表达。结果TIP30在19例正常脑组织神经胶质细胞及神经元胞质内均呈阳性表达;71例星形细胞瘤组织中,TIP30总阳性表达率为33．80％,随星形细胞瘤分化程度的降低,TIP30的表达逐渐降低,Ⅱ、Ⅲ和Ⅳ级星形细胞瘤中TIP30阳性表达率分别为52％、34．78％和13．04％。高级别星形细胞瘤（Ⅲ级＋Ⅳ级）中TIP30的阳性表达率显著低于其在低级别星形细胞瘤（Ⅱ级）中的阳性表达率（x^2=5．71,P〈0．05）;VEGF及由CD34确定的MVD在星形细胞瘤中表达均高于正常脑组织,且随星形细胞瘤病理级别升高表达逐渐增高;星形细胞瘤中TIP30与VEGF强阳性表达呈负相关关系（r=-0．428,P〈0．05）。而TIP30与MVD无明显相关性（r=-0．065,P〉0．05）。结论TIP30在正常脑组织中阳性表达率高于其在星形细胞瘤中阳性表达率,且随星形细胞瘤病理级别升高表达显著下降;星形细胞瘤中,VEGF的表达与TIP30的表达呈明显的负相关关系。