Expression of apoptosis and its related protein in astrocytic tumors

The relationship between malignant potential and apoptosis in astrocytic tumors has not been clearly defined, and further classification of astrocytic tumors is necessary. To elucidate the relationship between the histopathological grade of astrocytic tumors and apoptosis, we studied 25 cases of astrocytic tumors, comprising 10 cases of glioblastoma (GB), 7 cases of anaplastic astrocytoma (AA), and 8 cases of astrocytoma (AC). We detected apoptosis using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. We studied immunohistochemical expression of bcl-2 protein and p53 protein, which are apoptosis-related factors, and cell proliferative activity using Ki-67 antibody. No significant change was noted between apoptotic index and the histological grade of the tumors. In GB, apoptotic cell-rich foci were present at the pseudopalisading necrosis. No correlation between histopathological grades and expression of either p53 or bcl-2 was observed. In GB, however, poor distribution of bcl-2 was found in the areas of pseudopalisade formation. bcl-2 is one of the regulatory factors in the cell cycle and inhibits apoptosis. Expression of apoptosis had no correlation with histopathological grade. However, in GB, the distribution of apoptotic cells showed a correlation with bcl-2-poor foci. It was thought that apoptosis was one of the regulatory factors in the formation of pseudopalisading necrosis in GB.     

NF-κBp65、Bcl-2、Bcl-xL蛋白在胰腺癌中的表达及其与P53和凋亡指数的关系

背景与目的:核因子κB通过调控下游bcl-2家族基因表达参入细胞凋亡调节过程,而p53除了参入细胞周期调节外也参入依赖bcl-2基因的细胞凋亡调控。在胰腺癌中NF-κBp65、Bcl-2和Bcl-xL蛋白表达与p53和凋亡的关系还不清楚。本研究系统地分析了核因子κBp65及其下游的bcl-2和bcl-xL抑凋亡基因在胰腺癌(PC)中的表达以及与P53蛋白表达和凋亡指数(AI)的关系。方法:免疫组化法检测25例胰腺导管腺癌(PC)和9例正常胰腺组织(NP)中P53蛋白表达;Western印迹法分析NF-κBp65蛋白表达;RT-PCR分析Bcl-2和Bcl-XL蛋白表达,TdT酶介导的原位缺口标记(TUNNEL)法了解胰腺癌细胞凋亡情况(AI)。结果:P53在PC组织阳性率(56%,14/25),高于NP组织阳性率(P<0.00);NF-κBp65、Bcl-2和Bcl-xL在PC组织表达相对值分别为:1.06±0.16、0.79±0.13、0.76±0.24,分别高于NP组织:0.23±0.016、0.23±0.074、0.18±0.026(分别P<0.05);14例p53阳性PC中,NF-κBp65、Bcl-2和Bcl-Xl表达相对值分别为:1.32±0.23、0.92±0.33、0.82±0.21;11例p53阴性PC中,NF-κBp65、Bcl-2和Bcl-xL表达相对值分别为:0.78±0.15、0.54±0.19、0.71±0.28(分别P<0.05,P<0.05,P>0.05);NF-κBp65和Bcl-2分别与P53表达有明显的正相关性(分别P<0.01,P<0.05),Bcl-xL与P53无相关性(P>0.05),NF-κBp65与Bcl-XL表达正相关(P<0.01),而NF-κBp65与Bcl-2表达无相关性(P>0.05);胰腺癌平均AI为(15.4±6.48)%,NF-κBp65表达与AI负相关(r=-0.297,P<0.05),而Bcl-2、Bcl-xL与AI无相关性(r=-0.203,P>0.05;r=-0.156,P>0.05)。结论:胰腺癌中抗凋亡因子表达上调,凋亡指数主要决定于NF-κBp65蛋白水平;NF-κBp65通过对下游bcl-xL基因表达的调控参与胰腺癌凋亡过程;p53在凋亡调节过程中起重要作用。     

树鼩实验肝癌形成过程中p53、bcl-2蛋白表达及其与细胞凋亡之间的关系

目的:动态研究在树鼩肝癌形成过程中p53与bcl-2的蛋白表达以及它们之间的关系.方法:利用免疫组织化学SP法,对实验组35例树鼩肝癌形成过程中第30周、60周、肝癌组织及13例同期的空白对照组树鼩肝活检组织,进行p53、bcl-2蛋白的检测.结果:p53、bcl-2基因参与HCC的发生,在树鼩HCC形成过程中,它们的表达均呈递增趋势.结论:p53、bcl-2基因之间的表达无明显依存关系.p53对凋亡的影响并不显著,bcl-2的抗凋亡作用受Bax的影响,bcl-2/Bax比率更能准确地反映细胞凋亡的程度.     

乳腺癌组织中PCNA、bcl-2与p53基因蛋白表达

[目的]探讨乳腺癌、癌旁和正常乳腺组织中PCNA、bcl-2与p53基因蛋白表达的差异及其在乳腺癌变中的意义。[方法]用免疫组化法检测46例乳腺癌、癌旁组织和33例正常乳腺组织中PCNA、bcl-2与p53基因蛋白表达。[结果]①PCNA指数:乳腺癌与癌旁组织差异无显著性;乳腺癌和正常乳腺组织(46.03±8.76与32.13±6.78),乳腺癌旁和正常乳腺组织(42.90±7.92与32.13±6.78)差异均有显著性(P<0.01)。②bcl-2基因蛋白表达分值:乳腺癌、癌旁和正常乳腺组织分别为:0.62±0.47,0.91±0.58,1.56±0.84;分值大小顺序呈表达上升趋势。③p53基因蛋白表达分值:乳腺癌、癌旁组织和正常乳腺组织分别为:2.21±0.96,1.86±0.87,0.87±0.57;分值大小顺序表达呈下降趋势。④在乳腺癌组织PCNA指数与bcl-2呈中度负相关(rs=-0.537),与p53呈中度正相关(rs=0.628),bcl-2与p53呈中度负相关(rs=-0.476)。[结论]乳腺癌的发生、发展过程中PCNA和p53分值增大,bcl-2分值变小,预示组织恶性程度可能增加,对判定乳腺组织的良、恶性及预后具有重要临床价值。     

Histopathologic features and expression of Bcl-2 and p53 proteins in primary gastric lymphomas

The aim of this study is to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas which were reclassified according to the concept of mucosa associated lymphoid tissue (MALT). The resected specimens from 41 patients with primary gastric lymphoma were investigated retrospectively. Immunohistochemical study was done to analyze the immunophenotype and bcl-2 and p53 proteins expression. Twenty three of the cases had tumors mainly located in the antrum. Histologically, 12 were low grade and 20 were high grade B-cell lymphoma of MALT, 9 other B-cell nonHodgkin's lymphomas. Helicobacter pylori was identified in 72% of the cases. According to Musshoff's modification, most of the MALT lymphoma cases had stage I or II disease. There was significant difference between low and high grade cases, in respect to depth of invasion in gastric wall. Immunohistochemically, the neoplastic cells in all MALT lymphomas expressed B-cell phenotype. Bcl-2 protein was found to be expressed in 59% and p53 protein expression was detected in 72% of cases. Among the B-cell lymphoma of MALT, bcl-2 positivity decreased and p53 positivity increased significantly as the histological grade advanced. So, an inverse correlation was observed between the expression of bcl-2 and p53. In conclusion, most primary gastric lymphomas are low or high grade B-cell MALT lymphomas and appear to arise in MALT acquired as a reaction to Helicobacter pylori infection. Expression of bcl-2 and p53 in gastric lymphomas may be associated with transformation from low-grade to high-grade disease.     

肺癌组织中耐药相关蛋白和p53 bcl-2表达及其意义

目的:探讨肺癌组织中耐药相关蛋白和p53、bcl-2表达及其意义.方法:应用免疫组化技术检测治疗前73例肺癌组织标本中P-gp、MRP、LRP、GST-π、p53和bcl-2表达.结果:非小细胞肺癌组P-gp、LRP、MRP LRP、P-gp p53的蛋白表达明显高于小细胞肺癌组(P＜0.05).腺癌组MRP、LRP、MRP LRP、MRP LRP GST-π、MRP LRP P-gp GST-π蛋白阳性表达高于鳞状细胞癌组、小细胞肺癌组(P＜0.05),MRP GST-π共表达者高于鳞状细胞癌组(P＜0.01),P-gp-p53共表达者高于小细胞肺癌组(P＜0.05),bcl-2蛋白阳性表达低于鳞状细胞癌组、小细胞肺癌组(P＜0.05).鳞状细胞癌组P-gp、P-gp p53、P-gp bcl-2的蛋白表达明显高于小细胞肺癌组(P＜0.05).P-gp与p53、bcl-2蛋白阳性表达呈正相关(P＜0.05).p53与bcl-2蛋白阳性表达呈正相关(P＜0.01).MRP与GST-π蛋白阳性表达呈正相关(P＜0.05).结论:肺癌耐药为一多途径多基因参与的过程,P-gp、LRP、MRP、GST-π、p53、bcl-2表达及其共表达可作为监测肺癌细胞原发性耐药的指标.     

非小细胞肺癌端粒酶与p53、bcl-2、PCNA表达相关性

[目的]探讨非小细胞肺癌(NSCLC)组织中端粒酶活性和p53、bel-2、增殖细胞核抗原(prolif-erating cell nuclear antigen,PCNA)蛋白表达的相关性及其临床意义.[方法]采用PCR-ELISA检测端粒酶活性,SP免疫组化检测p53、bel-2、PCNA蛋白表达.[结果]NSCLC中端粒酶活性表达明显高于肺部良性肿瘤,且端粒酶活性与p53蛋白表达显著性相关(P＜0.01),而与bcl-2、PCNA蛋白表达无显著性相关.端粒酶活性与癌细胞分化程度呈显著性相关(P＜0.01),而与患者年龄、性别、吸烟、原发肿瘤大小(T)、淋巴结转移(N)、肺癌组织学类型均无显著性相关.[结论]端粒酶活性可做为NSCLC诊断及判断预后的较理想指标.端粒酶活性与p53基因之间可能存在着相互调控的机制.     

The p53 and mdm-2 genes in human testicular germ-cell tumors

Mutations in the p53 gene are common in many cancers. They have been documented to occur in about 55% of all cancers of 51 different cell and tissue types. These mutations are accompanied by overexpression of the p53 protein in the nucleus of the cell, and this protein has lost its tumor suppressor function. In this study, 25 testicular germ-cell (TGC) tumors were tested for p53 mutations and the level of p53 protein expression. While 67% of the tumors overproduced the p53 protein in the nucleus of 10-60% of their cells, in all cases the DNA sequence of exons 4-9 of the p53 gene was wild type. In this tumor type, there was apparently no selection pressure for p53 mutations. The mdm-2 gene resides on chromosome 12 (12q13-q14), a chromosome often altered in TGC tumors. mdm-2 gene amplification (2.5- to 10-fold) was detected in three (12%) of these TGC tumors. These three tumors, and eight additional TGC tumors, overexpressed mdm-2 mRNA. There was a good correlation between overexpression of p53 protein and overexpression of mdm-2 mRNA (P = 0.01). This may well result from the fact that the level of mdm-2 mRNA is regulated by the p53 level. These studies demonstrate that TGC tumors fail to be selected for p53 mutations but nonetheless frequently expressed high levels of wild-type p53 protein in the cell nucleus. Perhpas this produces the excellent response to radiation and chemotherapy of these tumors, which generally have a good prognosis. Wild-type p53 may mediate apoptosis in these cells in response to the DNA damage. © 1995 Wiley-Liss Inc.     

bcl-2、p53在皮肤肿瘤中的表达及意义

目的探讨bcl-2、p53在几种皮肤肿瘤中的表达及意义。方法采用流式细胞术(FCM)和免疫荧光技术对皮肤鳞状细胞癌(SCC)、恶性黑色素瘤(MM)、基底细胞癌(BCC)、色素痣(PN)bcl-2、p53蛋白的表达进行定量分析,以荧光指数(FI)作为定量表达指标。结果鳞状细胞癌、基底细胞癌的bcl-2、p53基因蛋白的FI值均显著性高于正常对照(P<0.05),基底细胞癌的bcl-2基因的FI值显著性高于鳞状细胞癌(P<0.05),而二者的p53基因蛋白的FI值无显著性差异(P>0.05);恶性黑色素瘤、色素痣的bcl-2、p53基因蛋白的FI值均显著性高于正常对照(P<0.05),恶性黑色素瘤的p53基因的FI值显著性高于色素痣(P<0.05),而二者的bcl-2基因蛋白的FI值无显著性差异(P>0.05)。结论鳞状细胞癌、恶性黑色素瘤、基底细胞癌、色素痣中均有bcl-2的表达,基底细胞癌bcl-2表达显著高于鳞状细胞癌,说明基底细胞癌的发生发展可能与细胞凋亡受抑密切相关;p53在恶性黑色素瘤的表达高于色素痣,说明p53为黑色素瘤的恶性标志,检测p53表达可以作为鉴别皮肤黑色素瘤恶性病变的辅助手段。     

缺氧对骨肉瘤细胞系MG-63 HIF-1α、p53 、bcl-2 及细胞凋亡的影响

 目的 了解缺氧环境对骨肉瘤MG-63细胞缺氧诱导因子HIF-1α、p53、bcl-2的表达及细胞凋亡的影响。方法 建立骨肉瘤细胞体外缺氧模型,观察不同缺氧时间段（8、16、24h）HIF-1α、p53、bcl-2的表达和细胞凋亡的情况。半定量RT-PCR方法检测HIF-1α、p53、bcl-2的表达水平;免疫组化（SP法）和免疫印迹（WesternBlot）检测HIF-1α、p53、bcl-2蛋白表达情况;流式细胞仪检测细胞凋亡率。结果 缺氧处理后,HIF-1α转录水平未见明显改变,蛋白表达水平随缺氧时间延长明显增强;而p53、bcl-2mR-NA及蛋白表达水平均显著增强,两者间存在一定的相关性;细胞凋亡率却未见明显增加。结论 在缺氧条件下,不能通过以HIF-1α为中介的p53依赖途径来诱导骨肉瘤MG-63细胞的凋亡,其机制可能与缺氧诱导野生型p53的突变或缺失使HIF-1α和bcl-2的过表达有关。     

乳腺癌新辅助化疗对凋亡相关基因p53、bcl-2的影响

目的 探讨乳腺癌新辅助化疗对凋亡相关基因p53、bcl-2表达的影响及其意义。方法 用免疫组织化学ABC法检测97例新辅助化疗（研究组）和同期76例未行新辅助化疗（对照组）的乳腺癌组织p53、bcl-2蛋白的表达，并结合5年无病生存率（DFS）进行分析。结果 研究组p53阳性率为28．9％（28／97），对照组为38．2％（29／76）；研究组bcl-2阳性率为40．2％（39／97），对照组为56．7％（43／76）；研究组5年DFS为74．2％（72／97），对照组为60．5％（46／76），两者比较均有显著差异。结论 新辅助化疗通过凋亡相关基因p53、bcl-2的表达影响预后。     

康莱特注射液诱发肾癌细胞凋亡及p53,bcl—2表达的研究

目的;探讨康莱特注射液抗肿瘤的作用机制。方法：利用ＭＴＴ法分析康莱特肾癌细胞的抑制作用,末端脱氧核苷酰转移酶法检测细胞凋亡,免疫组织化学法分析ｐ５３和ｂｃｌ－２基因表达的影响。结果：康莱特抑制肾癌细胞的ＩＣ５０为１９．３１μｌ／ｍｌ,５μｌ／ｍｌ,和１０μｌ／ｍｌ康莱特注射液具有诱发细胞凋亡的作用,细胞凋亡分别为３１．３０％和８９．７６％,康莱特浓度继续增加时,细胞凋亡的数量反而减少,１５μdispla     

Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue

The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.     

Apoptosis in transitional cell carcinoma of bladder and its relation to proliferation and expression of P53 and Bcl-2

Transitional cell carcinoma of bladder (TCC) is a relatively common cancer among men. Tumor progression is associated with expression or modulation of several gene products that control apoptosis and proliferation. Apoptosis is a negative growth regulatory mechanism in tumors. The aim of this study is to examine apoptosis and related regulatory molecular markers in a group of patients with TCC. Paraffinembedded tissues from 49 patients with TCC were examined for the expression of bcl-2, p53 and Ki-67 by immunohistochemistry. Apoptosis was detected by TUNEL method. Correlation between apoptotic index (AI), proliferation index (PI) and bcl-2 and p53 expression with each other and with pathological grade was determined. Apoptosis was observed in 28.1% of TCC cases. The mean AI of all cases was 13.7+/-24. No correlation was found between apoptosis and differentiation status of carcinoma. Bcl-2 expression was weakly detected in only one sample. P53 expression was detected in 26 of cases with mean staining index of 102+/-96. A significant correlation between p53 and Ki-67 staining indices was observed (r=0.521, p=0.001). Both p53 and Ki-67 expression showed a good association with the pathological grade (p=0.0001 and p=0.004, respectively). None of the markers showed significant correlation with AI and no correlation was found between the ratio of AI to PI and other parameters either. In conclusion, the frequency of apoptosis in TCC of bladder appears not to be associated with tumor grade, and with bcl-2, p53 and Ki-67 expression.     

Significance of p53, Bcl-2, and HER-2/<Emphasis Type="Italic">neu</Emphasis> protein expression in Omani Arab females with breast cancer

Recial disparity in the presentation of breast cancer and the outcome of its treatment is well established. However, the causes remain unexplained. The scarcity of reports about the prognostic significance of p53, bcl-2, and HER-2/neu in Arab females with breast cancer has been the impetus to this study. We evaluated the prognostic significance of altered expression of p53, bcl-2,HER-2/neu in Omani Arab females with non-metastatic breast cancer with correlation to other established prognostic factors. We have retrospectively analyzed the immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded blocks of 72 females diagnosed with invasive breast cancer between 1992 and 2002. The expression of the above proteins was correlated with other prognostic factors and univariate and multivariate analysis was carried out for all prognostic factors. Overexpression of p53 significantly correlated with younger age (<40), pre-menopausal status, poor differentiation with inverse correlation with bcl-2 expression. Expression of bcl-2 immunopostivity significantly correlated to low histological grade and positive estrogen and progesterone receptor status. On univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining resulted in worse survival outcome, but notHer-2/neu overexpression. Expression patterns of p53 and bcl-2 are independent predictors of survival in Omani Arab population which may help to stratify these patients into different risk groups.     

Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer

Summary Alterations in the mechanisms of apoptosis are responsible not only for the progression of breast cancer, but for different responses to treatment as well. Among the genes regulators of apoptosis, the tumor suppressor gene p53 and the bcl-2 gene have raised interest for their possible role as predictors of response to therapy and markers of prognosis. The purpose of our study was to prospectively analyze the prognostic value of the expression of p53 and bcl-2 genes in a series of 235 consecutive patients operated on for breast cancer at the Department of General Surgery and Surgical Oncology of the University of Siena, Italy.p53 and bcl-2 expression were evaluated by immunohistochemistry, their association with conventional clinicopathological factors was analyzed by univariate analysis and their prognostic impact was evaluated by multivariate analysis.p53 and bcl-2 were detected respectively in 15.7 and 75.7% of cases, and resulted significantly related to presence of estrogen receptors for p53 over-expression and presence of peritumor lymphovascular invasion (LVI) for bcl-2 expression.With a median follow-up of 79 months, an independent negative prognostic impact on disease free and overall survival was observed for presence of LVI, absence of bcl-2 expression and number of involved axillary lymphnodes. The expression of bcl-2 improved the prognosis of LVI positive tumors up to values similar to LVI negative cases, while its absence associated to presence of LVI resulted in a poor outcome with only 28% of patients alive at 8 years.These data may indicate that expression of bcl-2 is a marker of breast cancers with reduced capability of distant colonization, even in presence of LVI, and may be particularly useful in the clinical setting, allowing to identify a subset of patients with an high risk of relapse.     

P53 and bcl-2 in colorectal cancer arising in patients under 40 years of age: distribution and prognostic relevance

Young people (40 years of age) with colorectal cancer (CRC) represent a distinct subgroup with more aggressive disease behaviour compared to older patients. We evaluate whether p53 and bcl-2 could be useful in identifying young patients at higher risk of tumour progression. We reviewed 1340 CRC patients with 58 patients 40 years (4.2%). They had more frequent moderately or poorly differentiated mucinous adenocarcinomas (26% versus 12.3%, p = 0.03); higher advanced stage at diagnosis; shorter 5-year overall survival (49.8% versus 71%; p = 0.02); more frequent p53 positive (89.8% versus 72.6%, p < 0.05) and bcl-2 negative (88.0% versus 66.2%, p < 0.05) tumours; no difference in DNA content or proliferation indexes. Moreover, p53+ and bcl-2– resulted in being independent predictors of survival with shorter survival for the p53+/bcl-2– patients. Combining p53 and bcl-2, we could identify young CRC patients at higher risk of progression, who probably require development of a more sophisticated therapeutic approach based on identification of predictive factors.     

bcl-2、bax、P53在肺神经内分泌癌中表达的意义

背景与目的bcl-2和bax是调控细胞凋亡的主要因素,两者均为野生型p53的下游基因。本研究旨在分析肿瘤相关基因蛋白bcl-2、bax、P53、C-erbB-2和nm23-H1在肺神经内分泌癌中的表达与肿瘤生物学特点及患者生存时间的关系。方法采用HE染色及免疫组化SP法,对59例肺神经内分泌癌患者的预后和免疫表型进行分析,采用χ2检验、Kaplan-Meier生存分析和Cox风险模型分析。结果bcl-2、bax、P53、C-erbB-2、nm23-H1蛋白的阳性率分别为46%、56%、27%、14%、90%。bcl-2表达与肺神经内分泌癌类型、TNM分期及淋巴结有无转移有关(P值分别为0.037、0.011及0.020),但与肿瘤大小无明显相关性;bax表达则与肿瘤大小、种类、分期及淋巴结转移情况均无密切关系。单因素生存分析显示bcl-2、P53均与生存时间呈负相关(P值分别为0.0338和0.0375),nm23-H1与生存时间呈正相关(P值为0.0021)。Cox多因素生存分析发现,只有bcl-2与生存时间密切相关(P值为0.011)。结论bcl-2是肺神经内分泌癌独立的预后因子。     

Detection of apoptotic cells and immunohistochemical study of bcl-2 and p53 gene protein in primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma

In recent years, the study of apoptosis has become one of the hot subjects for cancer research. Recent research revealed that apoptosis might be associated with tumor initiation and development, cancer therapy and prognosis. A lot of genes have been found to involve in the apoptotic process, especially the p53 and bcl-2 gene. The mucosa associated lymphoid tissue type lymphoma (MALToma) is a sort of extra-nodal low-grade malignant lymphoma, which is different from primary nodal lymphomas in …