p63、Bcl-2和PCNA蛋白在B细胞非霍奇金淋巴瘤中的表达及意义

目的 探讨p63、Bcl-2和增殖细胞核抗原(PCNA)蛋白在B细胞非霍奇金淋巴瘤(B-NHL)发生、发展中的作用.方法 应用免疫组化染色法检测p63、Bcl-2及PCNA蛋白在50份B-NHL组织和20份反应性增生淋巴组织中的表达,分析各指标间及与B-NHL临床病理参数的关系.结果 p63、Bcl-2和PCNA蛋白在B-NHL组织中阳性表达率分别为60％、78％和80％,在反应性增生淋巴组织中的阳性表达率分别为5％、35％和35％,两两比较P均＜0.05；p63与Bcl-2、PCNA蛋白表达均呈正相关,r=0.453、0.800(P＜0.001或0.01)；三指标与患者年龄、B-NHL病理类型等临床病理参数均无明显关系(P均＞0.05).结论 p63可能与Bcl-2、PCNA协同参与B-NHL的发生,具体机制尚需进一步研究.     

胃癌的细胞凋亡及Bcl-2,P53蛋白表达研究

维持胃粘膜的正常结构依赖于胃粘膜细胞的丧失和增殖的动态平衡．这一平衡的失调被认为是胃癌发生发展的重要病理机制．本文选择了65例胃癌标本进行细胞凋亡的形态学观察和凋亡调控基因bcl-2和P53蛋白表达检测，以了解细胞凋亡及其调控基因bcl-2和P53与胃癌组织学及临床的关系．1对象和方法1.1对象65例标本均来自本院内镜活俭并经手术证实的胃癌患者．其中男42例，女23例．年龄22岁～70岁，平均51.5岁±7．1岁．组织学分型：高分化腺癌23例，中分化腺癌16例，低分化及未分化腺癌26例．Lauren分型：肠型36例，弥漫型29例．胃癌的临床分期按…     

胰腺癌Bcl-2,P53蛋白表达和细胞凋亡

目的　探讨ｂｃｌ２ ,ｐ５３ 基因和细胞凋亡在胰腺癌发病机制中的作用以及它们之间相互关系．方法　应用ＡＢＣ 免疫组化技术检测５０ 例胰腺癌中Ｂｃｌ２ 和Ｐ５３ 蛋白表达,运用原位末端标记法观察肿瘤中细胞凋亡数量．结果　Ｐ５３ 蛋白表达阳性率为５４ ％ ,临床Ⅰ期阳性率（２６－７ ％ ）却显著低于Ⅱ期（６１－１ ％ ） 和Ⅲ＋ Ⅳ期（７０－６ ％ ,Ｐ＜ ０－０５） ;Ｂｃｌ２蛋白表达阳性率为６４ ％ ,临床Ⅰ期阳性率（９３－３ ％ ） ,显著高于Ⅱ期（５５－６ ％ ） 和Ⅲ＋ Ⅳ期（４７－１ ％ ,Ｐ＜ ０－０５） ;组织学Ⅲ级癌细胞中凋亡指数明显高于Ⅰ,Ⅱ级（ Ｐ＜ ０－０５） ,Ｂｃｌ２ 蛋白阴性病例中凋亡指数明显高于Ｂｃｌ２ 阳性者（ Ｐ＜ ０－０１） ．结论　Ｂｃｌ２ 是通过抑制细胞凋亡参与肿瘤的生长过程,Ｂｃｌ２和Ｐ５３ 蛋白表达之间 存在密切负相关（τ＝ － ０－１７４７ ,Ｐ＜ ０－０５） ．     

BRCA1在弥漫性大B细胞淋巴瘤中的表达及意义

目的 探讨BRCA1在弥漫性大B细胞淋巴瘤的表达及与疾病预后的关系.方法 收集50例弥漫性大B细胞淋巴瘤标本和20例瘤周正常组织标本,采用免疫组化方法检测BRCA1在弥漫性大B细胞淋巴瘤和瘤周正常组织的表达,分析BRCA1表达与患者临床特点以及疾病预后的关系.结果 不同性别、年龄、发病部位、临床分期弥漫性大B细胞淋巴瘤患者BRCA1表达差异均无统计学意义（P均＞0.05）;弥漫性大B细胞淋巴瘤组织BRCA1表达的阳性率明显低于瘤周正常组织（x2=4.047,P＜0.05）;BRCA1表达阴性组的2年生存率高于阳性组（P＜0.05）.病变部位、临床分期、BRCA1表达、国际预后指数是影响弥漫性大B细胞淋巴瘤患者预后的独立变量.结论 BRCA1表达降低与弥漫性大B细胞淋巴瘤的发生有关,BRCA1可作为判断弥漫性大B细胞淋巴瘤预后的分子标志物.     

p53、p21WAF1、MDM2在NK/T细胞淋巴瘤中的表达及意义

p53是一个重要的抑癌基因,在调节细胞生长、凋亡及DNA修复中有重要的作用.其突变在淋巴瘤中很少,但p53蛋白在淋巴瘤中常过表达,尤其恶性度较高者.p21WAF1是细胞周期抑制因子.     

胃黏膜异型增生c-myc、bcl-2、P53的表达及其意义

胃黏膜异型增生是一种重要的癌前病变,在Padova国际分类中称非浸润性新生物,即由限制在基底膜内的肿瘤性上皮代替了正常的胃黏膜上皮。我们应用免疫组化技术检测c-myc、bcl-2、P53基因蛋白在胃黏膜异型增生中的表达,探讨它们与胃癌发生的关系。     

Cyclin Gl、Mdm2和P53在胃癌组织中的表达及相关性研究

目的探讨细胞周期蛋白G1(Cyclin G1)、鼠双微体基因(Mdm2)和P53在胃癌组织中的表达意义及相关性。方法采用免疫组织化学方法(SP法)检测54例胃癌组织中Cyclin G1、Mdm2和P53的表达,以20例正常胃黏膜组织作为对照。结果胃癌组织中Cyclin G1、Mdm2、P53的阳性表达率分别为62.96%、53.70%、44.44%,与正常组织对比,有显著性差异(P<0.05),Cy-clinGl、Mdm2的阳性表达率和表达强度与胃癌的分化程度相关。胃癌组织中Mdm2蛋白的表达与P53的表达呈正相关(r=0.307),而CyclinGl蛋白的表达与P53的表达无明显相关性。结论CyclinGl、Mdm2、P53的过表达在胃癌的发生、发展过程中起着重要的的作用。Mdm2可能是通过调控P53的活性而促进胃癌的发生、发展,Cyclin G1可能以不依赖P53的途径发挥作用。     

Bcl-2与NF-kB/p65在弥漫性大B细胞淋巴瘤中的表达及意义

目的探讨Bcl-2与NF-κB/p65蛋白在弥漫性大B细胞淋巴瘤(DLBCL)中的表达及意义。方法采用免疫组化方法检测DLBCL患者Bcl-2和NF-κB/p65蛋白的表达,分析二者与DLBCL临床特征、疗效及预后的关系。结果Bcl-2和NF-κB/p65蛋白在DLBCL中的表达率为51.5%和38.7%,二者表达有相关性;Bcl-2与NF-κB/p65蛋白在DLBCL中的表达与临床分期、疗效及预后有关。结论Bcl-2、NF-κB/p65蛋白检测可作为DLBCL患者不良临床特征及预后较差的指标,并有助于指导个体化药物治疗。     

肝细胞癌P53，Bcl-2蛋白的表达和细胞凋亡

目的探讨肝细胞癌（ＨＣＣ）中细胞凋亡情况及其与Ｐ５３和Ｂｃｌ２蛋白表达的关系．方法细胞凋亡采用原位细胞凋亡检测法Ｐ５３和Ｂｃｌ２蛋白表达采用免疫组化方法．细胞凋亡与Ｐ５３，Ｂｃｌ２蛋白表达的关系采用双标记法进行检测．结果ＨＣＣ７０例，癌组织和癌周组织中细胞凋亡指数（１０００个细胞中）分别为３６±２０和１０６±３６．Ｂｃｌ２和突变型Ｐ５３蛋白检出率分别为２２９％和４２９％．Ｂｃｌ２主要表达在癌周组织中，抑制肝细胞凋亡；而Ｐ５３则仅表达在癌组织，抑制癌细胞凋亡．双染色显示细胞凋亡与Ｐ５３或Ｂｃｌ２不同时在一个细胞中表达．结论ＨＣＣ癌细胞凋亡减弱．突变型Ｐ５３蛋白是癌细胞凋亡减弱的主要原因，而Ｂｃｌ２则可能在维持ＨＣＣ的肝脏功能方面具有重要作用．     

p27kip1和p57kip2与CyclinD1在急性白血病的表达及其临床意义

目的:探讨p27kip1和p57kip2与CyclinD1在急性白血病中的表达情况及其临床意义.方法:采用免疫组化S-P法检测39例急性白血病及10例正常对照者骨髓中p27kip1和p57kip2与CyclinD1蛋白的表达情况,并结合临床病理资料进行分析.结果:p27kip1和p57kip2与CyclinD1蛋白在急性白血病患者的阳性表达率分别为31%、33%、54%,在对照组表达率为70%、40%、0.p27kip1与cyclinD1在白血病与对照组中的表达差异有统计学意义.在37例接受化疗的急性白血病中,p27kip1和p57kip2阳性表达组化疗后的缓解率(66%、69%)明显高于p27kip1和p57kip2表达阴性组的缓解率(32%、29%),其差异有统计学意义(P＜0.05).p57kip2与CyclinD1在白血病中的表达具有正相关性.结论:p27kip1和p57kip2与CyclinD1在急性白血病患者中存在异常表达其蛋白的表达水平可能会影响化疗疗效.     

Prognostic significance of bcl-2, bax,and p53 expression in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLCL) exhibits heterogeneous clinical features and varies markedly in response to treatment and prognosis. Because apoptosis-related proteins may play an important role in predicting the prognosis of DLCL, the current study investigated the prognostic significance of a high level of bcl-2, bax, and p53 expression in relation to clinical characteristics in patients with DLCL. Paraffin-embedded specimens from 94 patients with de novo DLCL were analyzed immunohistochemically for bcl-2, bax, and p53 gene expression. Cases with a positive immunohistological stain in more than 50% of the tumor cells were considered to have DLCL-positive expression. Patients were treated optimally, i.e., with radiotherapy including brief cycles of CHOP or CHOP-like regimens for patients with stage 1-2A diseases and with at least 6 cycles of CHOP or CHOP-like regimens for stage 2B-4 diseases. The responses to therapy and survival were then analyzed in 94 uniformly staged patients. bcl-2 expression was identified in 24 patients (26.4%), bax expression in 35 patients (37.6 %), and p53 expression in 21 patients (22.6%). bax expression proved to be a statistically significant prognostic factor in predicting the overall survival (OS) (P = 0.0015) and disease-free survival (DFS) (P = 0.0052), regardless of other clinical factors or immunohistological results. There was no significant difference in the OS (P = 0.0682) or DFS (P = 0.088) between the bcl-2-positive (n = 24) and bcl-2-negative (n = 67) groups. However, bcl-2 expression was found to be unfavorably associated with the OS (P = 0.0054) in a confined group with low (n = 51) or low intermediate (n = 22) IPI scores. The expression of p53 exhibited no statistical correlation with the OS or DFS. A multivariate analysis revealed that IPI score, bulky mass, and bax expression were all significantly associated with the DFS or OS. bax and bcl-2 should be considered as independent biologic prognostic parameters in DLCL, thereby aiding in the identification of patient risk groups. As such, bcl-2-positive patients with a low or low intermediate IPI score, or without a high level of bax expression could be candidates for more intensive therapy or alternative therapeutic approaches.     

p27^kipl和p57^kip2与CyclinD1在急性白血病的表达及其临床意义

目的:探讨p27kipl和p57kip2与CyclinD1在急性白血病中的表达情况及其临床意义。方法:采用免疫组化S-P法检测39例急性白血病及10例正常对照者骨髓中p27kipl和p57kip2与CyclinD1蛋白的表达情况,并结合临床病理资料进行分析。结果:p27kipl和p57kip2与CyclinD1蛋白在急性白血病患者的阳性表达率分别为31%、33%、54%,在对照组表达率为70%、40%、0。p27kipl与cyclinD1在白血病与对照组中的表达差异有统计学意义。在37例接受化疗的急性白血病中,p27kipl和p57kip2阳性表达组化疗后的缓解率(66%、69%)明显高于p27kipl和p57kip2表达阴性组的缓解率(32%、29%),其差异有统计学意义(P<0.05)。p57kip2与CyclinD1在白血病中的表达具有正相关性。结论:p27kipl和p57kip2与CyclinD1在急性白血病患者中存在异常表达其蛋白的表达水平可能会影响化疗疗效。     

细胞周期蛋白D1、p16蛋白在胆汁反流性胃炎中的表达及意义

目的 探讨细胞周期蛋白D1(CyclinD1)、p16蛋白在胆汁反流性胃炎(BRG)中的表达,探寻BRG与胃癌的相关性。方法 应用过氧化物酶标记的SP染色法进行免疫组织化学染色以检测癌基因CyclinD1及抑癌基因p16蛋白在正常胃黏膜、BRG、癌旁组织、胃癌中的表达。结果 CyclinD1在正常胃黏膜、BRG、癌旁组织、胃癌中的阳性表达率逐渐升高,在BRG中的阳性表达率显著高于正常胃黏膜组织,差异有统计学意义(P0.05)。p16在正常胃黏膜、BRG、癌旁组织、胃癌中的阳性表达率逐渐降低,在BRG中的阳性表达率显著低于正常胃黏膜组织,差异有统计学意义(P0.05)。但CyclinD1、p16蛋白在BRG、癌旁组织中的表达差异无统计学意义(P0.05)。结论 BRG可能有癌变倾向,且CyclinD1、p16蛋白可能参与了其向胃癌发生发展的过程。     

Clinical significance of co-expression of CD21 and LFA-1 in B-cell lymphoma

We previously reported that the prognosis of CD21-positive diffuse large B-cell lymphoma (DLBCL) is significantly favorable to that of CD21-negative DLBCL (Otsuka et al. in Br J Haematol 127:416–424, 2004). In this study, we attempted to clarify the biological significance of CD21 expression in B-cell lymphoma (BCL) by performing in vitro experiments using CD21 transfection into a CD21-negative lymphoma cell line and analyzing clinical data from lymphoma samples. Established clones of CD21 transfectants showed homotypic aggregation in suspension culture. Analysis of integrin expression revealed that LFA-1 appeared to be expressed on CD21 transfectants, and the cell aggregation was abrogated by anti-LFA-1 antibody. The CD21 transfectants could adhere to plastic plates coated with ICAM-1. Moreover, flow cytometry and/or immunohistochemical analyses of clinical BCL samples (n = 29) revealed positive for CD21 in all cases; LFA-1 was also expressed without exception. All BCL cells isolated from cavity fluids (n = 10) failed to express both CD21 and LFA-1. These data suggest that CD21 is tightly related to LFA-1 expression in BCL and the absence of CD21/LFA-1 expression is associated with pleural/peritoneal fluid involvement by BCL, a potential indicator of disease progression of BCL.     

KLF6、p21^WAF1/CIP1、CyclinD1在结直肠癌中的表达及意义

目的研究转录因子KLF6、p21WAF1/C IP1及Cyc linD1在结直肠癌中的表达及意义。方法应用免疫组化Envision法对58例结直肠癌组织、20例结直肠黏膜慢性炎症组织中的KLF6、p21WAF1/C IP1及Cyc linD1蛋白表达进行检测。结果结直肠癌组织KLF6、p21WAF1/C IP1及Cyc linD1蛋白表达率均与结直肠黏膜慢性炎症组织比较有统计学差异（P〈0.05）;KLF6、p21WAF1/C IP1及Cyc linD1蛋白在结直肠癌组织中的表达与其浸润深度及预后有关（P〈0.05）。结论 KLF6、p21WAF1/C IP1及Cyc linD1在结直肠癌的发生发展中可能起重要作用。     

幽门螺杆菌感染与胃癌及癌前病变中c-myc、p53、C-erbB-2及bcl-2蛋白表达关系的研究

目的 观察胃癌、癌前病变中幽门螺杆菌(Hp)感染情况及其与c-myc、p53、c-erbB-2、bcl-2在胃癌及癌前病变中的表达关系,探讨Hp在胃癌、癌前病变发生及发展中的作用以及探索从癌前病变到癌变过程中的基因变化规律.方法 放大内镜及超声内镜检查收集103例胃黏膜标本,用免疫组织化学染色方法检测Hp感染及不同组织间c-myc、p53、c-erbB-2、bcl-2的表达.结果 c-myc、p53、c-erbB-2和bcl-2阳性表达率在胃癌组及癌前病变组中呈过度表达,与正常对照组相比有显著性差异(P<0.05).此外,Hp感染组c-myc、p53、c-erbB-2及bcl-2同时表达者为5例(9.4%);与无Hp感染组相比有显著性差异(P<0.01).结论 胃癌及癌前病变中组织存在c-myc、p53、c-erbB-2、bel-2多个表达,与Hp感染密切相关.     

Heterogeneity in cell proliferation and expression of p53 and bcl-2 during the indolent phase of germinal centre cell lymphoma: an explanation for clinical variability

Summary. Germinal centre cell lymphomas (GCCL) show a wide range of clinical outcomes from persistent indolent disease to large cell transformation. To investigate possible mechanisms of this heterogeneity, a combined morpho-metric and immunohistological study of p53, bcl-2 and cell proliferation was carried out. There was wide variation in p53 expression between biopsies and between individual follicles in the same tumour. A similar pattern of variation was seen using the cell-cycle marker MIB1, but this did not correlate with p53 expression. Even in cases in which a t(14:18) was demonstrated by PCR, variation occurred in the number of cells expressing bcl-2.
On the basis of these results, we suggest that the probability of the clonal expansion of GCCL tumour cells carrying additional genetic abnormalities depends on a complex interaction of cell proliferation with p5 3 and bcl-2 expression, and that this may account for variation seen in the clinical behaviour seen in this group of tumours.     

p53 expression,K-ras gene mutation and microsatellite instability in gastric B-cell lymphomas

BACKGROUND AND AIMS: Genetic mechanisms involved in the development of gastric B-cell lymphomas remain unclear. The aim of the present study was to clarify the roles of mutations of the p53 and K-ras genes, and microsatellite instability (MSI) in the development of gastric B-cell lymphomas. METHODS: We investigated p53 immunoreactivity, mutations of the K-ras gene, and MSI in 27 gastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type (MZBCL) and 24 diffuse large B-cell lymphomas (DLBCL). p53 immunoreactivity was examined using a monoclonal antibody, DO-7. Mutation of the K-ras gene was detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. MSI was examined at five microsatellite loci with a microsatellite assay. Cases were classified as having high-frequency MSI (MSI-H) (>/= 2 loci showing instability), low-frequency MSI (MSI-L) (only one locus showing instability), or as microsatellite stable. RESULTS: p53 immunoreactivity was detected in 1 of 16 (6%) MZBCL and 8 of 19 (42%) DLBCL. Frequency of p53 immunoreactivity in DLBCL was significantly higher than that in MZBCL (P = 0.018). MSI-H was detected only in 1 of 20 (5%) DLBCL. None of the cases examined showed mutation of the K-ras gene. CONCLUSIONS: These data suggest that mutations of the p53 gene may play an important role in the development of gastric DLBCL, and that mutations of the K-ras gene and MSI may be involved in little part of the development of gastric B-cell lymphomas.