大肠癌中EGFR、nm23、Ki-67的表达及临床意义

目的 探讨EGFR、nm23及Ki-67蛋白在大肠癌组织中的表达情况及其生物学意义.方法 采用高通量的组织芯片技术及免疫组织化学SP法检测115例大肠腺癌组织、19例大肠腺瘤组织和12例正常大肠组织中EGFR、nm23及Ki-67蛋白的表达.结果 在正常黏膜、腺瘤及腺癌组织中EGFR蛋白的阳性表达率分别为25%、47.37%、71.30%,nm23的阳性表达率分别为83.3%、68.42%和41.74%,Ki-67的阳性表达率分别为25%、36.82%、63.48%.腺癌组织中EGFR、Ki-67的表达明显高于腺瘤及正常黏膜组织,而nm23的后两者表达要明显高于前者,且均具有统计学意义(P<0.05).结论 EGFR、nm23、Ki-67的表达分别与大肠腺癌的分化、浸润程度、Dukes分期及淋巴结转移密切相关,可为大肠癌的早期诊断、治疗及预后的判断提供可靠的参考依据.     

不同类型淋巴瘤中survivin和bcl-2的表达及意义

目的　探讨检测抗凋亡基因survivin和bcl- 2在不同类型淋巴瘤的表达及对淋巴瘤诊断和分型的意义。方法　石蜡标本制作组织芯片,应用免疫组化S P法检测219例淋巴瘤及13例反应性增生淋巴结石蜡标本中survivin和bcl 2表达;同时应用RT PCR技术检测18例淋巴瘤、2例淋巴结反应性增生survivin和bcl- 2mRNA表达,并进行半定量分析。结果　survivin在弥漫性大B细胞淋巴瘤(diffuselargeBcelllymphoma,DLBL) (88. 6%, 70 /79)、淋巴母细胞淋巴瘤(lymphoblasticlymphoma,LBL) (92 3%, 12 /13)、伯基特淋巴瘤(Burkitt slymphoma,BL) (2 /2)有较高的表达;而在滤泡性淋巴瘤(follicularlymphoma,FL)、黏膜相关淋巴组织边缘区B细胞淋巴瘤(extranodalmarginalzoneB celllymphomaofmucosa associatedlymphoidtissuelymphoma,MALTL)和淋巴结边缘区B细胞淋巴瘤(marginalzonelymphoma,MZL)中表达较低,且多为弱阳性。高表达组与低表达组之间差异有统计学意义(P<0. 01 )。bcl- 2在小淋巴细胞淋巴瘤(smalllymphocyticlymphoma,SLL)、套细胞淋巴瘤(mantlecelllymphoma,MCL)、外周T细胞淋巴瘤(peripheralTcelllymphoma,PTL)、间变性淋巴瘤(anaplasticlargecelllympho ma,ALCL)、DLBL和FL有较高的表达,但各组间差异无统计学意义(P     

抗凋亡基因bcl-2在大肠癌中的表达及意义

本研究采用免疫组织化学ＳＡＢＣ法对７７例大肠癌ｂｃｌ－２进行了检测。结果表明，在７７例大肠癌中，ｂｃｌ－２阳性６７例（８７．０１％）；在作为对照的５７例癌周组织中，ｂｃｌ－２阳性占４７例（８２．４５％）；在４６例高分化的大肠癌中，比１５例低分化腺癌表达要强（Ｐ＜０．０１）。结论：ｂｃｌ－２在绝大部分大肠癌中都有表达，这表明其参与了大肠癌的凋亡调控，其表达与大肠癌的分化有关。     

VEGF、survivin、bcl-2在膀胱移行细胞癌中的表达和意义

肿瘤血管形成过程复杂,其中血管内皮细胞生长因子（VEGF）发挥重要作用。膀胱移行细胞癌发生、发展受多种基因调控。survivin蛋白作为凋亡抑制蛋白（inhibitor of apoptosis protein,IAP）家族中的IAP蛋白,其结构独特,与多种肿瘤的恶性程度和预后密切相关。bcl-2基因具有抑制细胞凋亡和延长细胞存活的功能,它不加速细胞分裂、增殖,而是促进细胞生存。我们用免疫组化技术研究VEGF、survivin、bcl-2在膀胱移行细胞癌组织中表达,并分析其相关性,为膀胱移行细胞癌的诊断治疗及预后判断提供依据。[第一段]     

胃癌组织中bcl-2表达与预后的关系

胃癌是严重危害人类健康的常见恶性肿瘤之一,癌细胞浸润、淋巴结转移是胃癌术后复发和化疗失败的主要原因。为阐明bcl-2基因在胃癌发生、发展及预后过程中的作用,检测60例胃癌bcl-2表达情况,探讨与胃癌发展及预后的关系。1材料与方法1.1病例来源60例胃癌均取自张家口地区1996~2     

人肺癌细胞凋亡与p53、bcl-2、Bax的表达

目的：探讨人肺癌组织细胞自发凋亡的发生,ｐ５３基因及凋亡相关基因ｂｃｌ－２、Ｂａｘ在肺癌组织中的表达及与肺癌细胞凋亡和生物学行为的关系。方法：用甲基绿－派诺宁染色检测５０例肺癌组织切片中凋亡细胞,ＬＳＡＢ免疫组化法检测ｐ５３和Ｂａｘ的蛋白表达,原位杂交方法检测ｂｃｌ－２ ｍＲＮＡ的表达。结果：１００％小细胞肺癌凋亡发生数１０个／ＨＰＦ,２１％的肺鳞癌和１５％的肺腺癌凋亡发生数〉１０个／ＨＰＦ。ｐ５     

大肠癌及癌旁肠黏膜组织中人子宫颈癌癌基因mRNA及蛋白的表达

目的探讨HCCR-1 mRNA及HCCR-1蛋白在人大肠癌、癌旁组织及远端正常肠黏膜组织中的表达,及其临床病理学意义。方法应用RT-PCR方法检测84例大肠癌、癌旁组织及15例远端正常肠黏膜组织中HCCR-1 mRNA水平,应用Westernblot技术检测84例大肠癌、癌旁组织及15例远端正常肠黏膜组织中HCCR-1蛋白的表达水平,应用免疫组化SP法检测84例大肠癌、癌旁组织及15例远端正常肠黏膜组织、30例管状及绒毛管状腺瘤组织中HCCR-1蛋白的表达,分析HCCR-1表达水平与大肠癌临床病理特征的相关性。结果 HCCR-1 mRNA在人大肠癌及癌旁肠黏膜组织中均有表达。HCCR-1蛋白在癌旁肠黏膜组织和管状及绒毛管状腺瘤组织的阳性率分别为38%(32/84)、30%(9/30),两者差异无统计学意义(P>0.05),在大肠癌中的阳性率为81%(68/84),明显高于癌旁肠黏膜组织和管状及绒毛管状腺瘤的阳性率(P<0.05)。大肠癌HCCR-1蛋白的高表达与肿瘤浸润深度呈明显正相关(P=0.007),与肿瘤是否转移无关(P>0.05)。结论人大肠癌存在HCCR-1蛋白的高表达,其与大肠癌的恶变演进有关。HCCR-1 mRNA的表达可能影响大肠癌的发生、发展。     

自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌中的表达及意义

目的检测自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌、大肠腺瘤及正常大肠黏膜中的表达情况,探讨其与大肠癌发生、发展的相关性及意义。方法应用组织芯片技术和免疫组化SP法检测12例正常大肠黏膜、29例大肠腺瘤及115例大肠癌组织中LC3、Beclin-1、p53及BCL-2蛋白的表达水平,并结合临床病理因素进行分析。结果 LC3在大肠癌中的阳性率高于大肠腺瘤和正常大肠黏膜(P<0.01),且与大肠癌的组织学分化程度相关(P<0.05)。Beclin-1在大肠癌、大肠腺瘤组织中的表达高于正常大肠黏膜(P<0.01),但与大肠癌的组织学分化程度、Dukes分期及淋巴结转移无关(P均>0.05)。p53及BCL-2在正常大肠黏膜、大肠腺瘤及大肠癌中的表达逐渐增高(P<0.01),且与大肠癌的Dukes分期和淋巴结转移相关(P均<0.05)。经Spearman秩相关检验,Beclin-1蛋白与p53蛋白相关系数为0.224 3,成正相关表达(P<0.05)。结论在大肠癌中,自噬活性的上调与凋亡能力的下调并存;自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌的发生、发展中起协调作用,对其联合检测有助于了解和判断大肠癌的进展程度及患者的预后情况。     

甲状腺乳头状癌中Fas-L和bcl-2表达及其意义

目的　探讨甲状腺乳头状癌细胞凋亡相关蛋白Fas L和bcl 2的表达及其意义。方法　采用免疫组化S P法检测 8例正常甲状腺组织和 2 7例甲状腺乳头状癌中凋亡相关蛋白的表达 ,并分析凋亡相关蛋白的表达与甲状腺乳头状癌发生发展的关系。结果　甲状腺乳头状癌均有强弱不等的Fas L及bcl 2表达 ,有被膜浸润及术后复发者Fas L呈高表达 ,阳性率为81 8% ,预后较好者则为 31 2 % ,二者间差异有显著性 (P <0 0 5 ) ;甲状腺乳头状癌的有明显间质浸润及缺少淋巴细胞反应和邻近正常组织的癌细胞Fas L表达均较强。有被膜浸润及术后复发和预后较好者bcl 2呈高表达 ,阳性率分别为 87 5 % ,4 5 5 % ,二者间差异有显著性 (P <0 0 5 )。结论　甲状腺乳头状癌Fas L的高表达与肿瘤浸润性有关 ,Fas L表达愈强预示其预后不良。甲状腺乳头状癌bcl 2的高表达与其浸润性较弱有关。     

大肠癌伴血吸虫病组织中AKT1、survivin的表达及意义

目的 探讨AKT1、survivin在大肠癌伴血吸虫病中的表达及其临床意义.方法 运用免疫组化SP法检测75例伴与不伴有血吸虫病的大肠腺癌、40例伴与不伴有血吸虫病的正常大肠黏膜中AKT1、survivin的表达.结果 AKT1、survivin分别在正常大肠黏膜、大肠腺癌之间的阳性表达差异有统计学意义(P<0.01,P<0.01);survivin阳性表达率与患者肿瘤分化程度、生存时间有关(P<0.05);AKT1与survivin呈正相关(P<0.01); AKT1、survivin在大肠腺癌伴与不伴血吸虫病两组病例之间的阳性表达差异无统计学意义(P值均>0.05).结论 AKT1、survivin在大肠癌癌变过程中发挥重要的作用,促进了大肠癌的发生、发展.大肠腺癌伴血吸虫病与不伴血吸虫病两组病例中AKT1、survivin表达无明显差异,提示在大肠癌癌变过程中血吸虫没有对这两项指标产生明显影响.     

柯萨奇病毒B3感染HeLa细胞后Bax和Bim的表达*

 目的：观察HeLa细胞感染柯萨奇病毒B3 (CVB3)后Bax和Bim mRNA和蛋白的表达。方法：将HeLa细胞分为未予以CVB3感染的对照组和予以CVB3感染的病毒组,取3 h、6 h、9 h、12 h和24 h 的细胞,采用RT-PCR和Western blotting分别检测Bax和Bim mRNA和蛋白的表达。结果：Bax和Bim　mRNA在对照组和病毒组HeLa细胞中均有表达,在病毒组和对照组中Bax和Bim mRNA的表达在各自组内均无显著差异（P＞0.05）,但在24 h Bax和Bim在病毒组mRNA的表达低于对照组（P＜0.05）。Bax和Bim蛋白表达在对照组中各时点均有表达,但无显著差异（P＞0.05）。病毒组Bax蛋白在24 h表达下降,差异有统计学意义（P＜0.05）,且病毒组表达明显低于对照组（P＜0.05）;Bim蛋白的表达随感染时间延长而下降（P＜0.05）,9 h、12 h和24 h表达病毒组低于对照组（P＜0.05）。结论:Bax和Bim在CVB3感染诱导的HeLa细胞凋亡早期发挥作用。     

Expression of bcl-2, Bax and Fas in oxyphil cells of Hashimoto thyroiditis

Immunoreactivity for bcl-2, Bax and Fas was analysed in 16 cases with Hashimoto thyroiditis. Bcl-2-expression was constantly seen in regular thyrocytes and in the mantle-zone of lymphofollicular infiltrates. However, thyrocytes in the vicinity of lymphoid infiltrates and, especially, mitochondria-rich oxyphil cells exhibited reduced staining or none at all for bcl-2. Bax was found to be weakly reactive or negative in normal thyrocytes and was not up-regulated in bcl-2-deficient epithelial cells. In contrast, expression of Fas was markedly increased both in typical thyrocytes and in oxyphil cells within areas of lymphocytic infiltration. In conclusion, focal lack of bcl-2 expression together with up-regulation of Fas is a constant feature of Hashimoto thyroiditis. The reaction pattern of oxyphil cells is identical to that of affected typical thyrocytes without proliferation of mitochondria. Loss of bcl-2 with up-regulation of Fas is therefore likely to precede oncocytic change. Whether these alterations are involved in the process of oncocytic transformation remains to be clarified, however. Received: 25 June 1999 / Accepted: 14 January 1999     

膀胱癌中p53、c—myc和bcl—2的表达及意义

目的：研究癌基因和抗癌基因蛋白产物在膀胱移行细胞癌组织中异常表达与病理分级,临床分期间关系。方法：应用免疫组化S－P法检测96例膀胱移行细胞癌中p53,c-myc和bcl-2的表达水平。结果：96例膀胱移行细胞癌中p53,c-myc和bcl-2的阳性表达率分别为60．4％,68．8％和81．3％,结果表明,p53,c-myc和bcl-2异常表达与膀胱移行细胞癌的分级和分期间差异有统计学意义。结论：p53,c-myc和bcl-2表达在膀胱癌的发生发展中起重要作用。在膀胱癌变过程中,有多种癌基因的变化。     

Expression of bcl-2 oncoprotein in transitional cell carcinoma of the upper urinary tract

 We investigated the immunoreactivity for bcl-2 oncoprotein in 154 cases of transitional cell carcinoma of the upper urinary tract (TCC-UUT) and its relation with the immunoreactivity for p53 oncoprotein and proliferating cell nuclear antigen (PCNA) immunoreactivity. Immunohistochemically, bcl-2 oncoprotein was recognized as positive in 29.2% of the samples. The immunoreactivity for bcl-2 oncoprotein was significantly (P < 0.05) correlated only with stage, though there was a borderline correlation (P = 0.050) with PCNA immunoreactivity. Furthermore, in invasive TCC the immunoreactivity for bcl-2 oncoprotein was associated with PCNA immunoreactivity (P < 0.041). The 5-year disease-free and overall survival rates were 55.7% and 71.5%, respectively. A univariate analysis of survival revealed that stage, grade, pattern of growth, immunoreactivity for p53 oncoprotein, and PCNA immunoreactivity each had a significant effect on disease-free and overall survival rates, whereas the immunoreactivity for bcl-2 oncoprotein had no significant effect on either rate. In the final models of the multivariate analysis, stage was found to be the only prognostic factor for disease-free survival and for overall survival. Detection of immunoreactivity for bcl-2 oncoprotein appears to be of no real value in deciding the prognosis of TCC-UUT. Received: 3 July 1997 / Accepted: 29 October 1997     

Expression of the apoptosis suppressing bcl-2 protein in transitional cell bladder tumours

The expression of bcl-2 protein was studied by immunohistochemistry using a monoclonal antibody in 158 cases of transitional cell bladder tumours. The bcl-2 protein was expressed in basal cells in normal transitional epithelium and 68% of the transitional cell tumours showed bcl-2 positivity in the basal cells. The expression of bcl-2 in basal cells was positively correlated to over-expression of epidermal growth factor receptor in tumour cells. The expression of bcl-2 in non-basal cells was weak in 20% and strong in an additional 13% of tumours. The expression of bcl-2 in non-basal cells was positively correlated to T-category, M-category, grade, papillary status, DNA ploidy, S phase fraction, mitotic index, nuclear area and over-expression of epidermal growth factor receptor. Recurrence-free interval of Ta-T1 tumours was related to bcl-2 positivity in non-basal cells. Tumours with bcl-2 positive non-basal cells had an unfavourable prognosis but, in multivariate analysis, expression of bcl-2 had no independent prognostic value.     

bcl-2和p53表达在结直肠癌预后评估中的价值

目的　探讨bcl 2和 p5 3表达水平与结直肠癌肿瘤生物学特征及其预后的关系。 方法　应用免疫组化S P法 ,检测93例结直肠癌标本中bcl 2与p5 3蛋白的表达 ,并与临床病理特征进行相关分析。结果　bcl 2蛋白在结直肠癌的阳性表达率为 5 7 0 % (5 3/ 93) ,与淋巴结转移呈负相关 (P <0 0 1) ,p5 3表达阳性率为 4 3% (4 0 / 93) ,与淋巴结转移无相关 (P >0 0 5 ) ,但p5 3表达阳性患者的预后差于 p5 3阴性组 (P =0 0 1)。当分析bcl 2和 p5 3联合表达时 ,Dukes分期及淋巴结转移各组间有差异 (P <0 0 5 )。其中bcl 2 (+) / p5 3(- )表达形式多见于DukesA和B期肿瘤 (4 1 0 % ,2 3/ 5 6 )。经Cox模型多因素分析结果表明 ,淋巴结转移 (P <0 0 1)和 p5 3表达 (P <0 0 1)是结直肠癌独立预后影响因素。其他指标 ,包括bcl 2和 p5 3联合表达情况等均未显示出统计学意义。结论　bcl 2和p5 3表达水平可提示结直肠癌的生物学行为 ,但bcl 2的表达与淋巴结转移状况相关不是一个单独作用的预后指标 ,而 p5 3虽与其它生物学特性关系不大 ,却是一个相对独立的结直肠癌预后指标。     

肝癌中bcl-2和bax基因的表达及其关系

目的：为了探讨巨细胞凋亡基因在肝癌发生中的作用。方法：利用免疫组化ＡＢＣ法,检测了肝癌中细胞凋亡抑制基因ｂｃｌ－２,促细胞凋亡基因ｂａｘ的表达。结果：ｂｃｌ－２以及ｂａｘ的个体阳性率均比正常对照组有显著性提高;肝癌组中ｂｃｌ－２和ｂａｘ的表达呈正相关,但无显著性。结论：ｂｃｌ－２表达抑制细胞凋亡,导致肝癌发生;ｂａｘ表达促进细胞凋亡,使肿瘤维持在高殖状态 。     

丙酸睾酮对大鼠胸腺细胞凋亡及胸腺中Bcl-2、Bax表达的影响

目的探讨丙酸睾酮在大鼠胸腺退化过程中的作用及其对大鼠胸腺中Bcl-2和Bax表达的影响。方法雄性大鼠去势后给予丙酸睾酮皮下注射,分别于注射后第1、4、7天取材,用半薄切片甲苯胺蓝染色检测胸腺细胞凋亡情况,免疫组织化学法检测胸腺组织中Bcl-2和Bax的表达情况,采用t检验进行统计学处理。结果丙酸睾酮处理组大鼠胸腺组织中可发现较多的凋亡细胞和凋亡小体;去势组大鼠胸腺组织中Bcl-2表达量明显高于假手术组（P〈0.001）,丙酸睾酮处理后Bcl-2表达量明显减少（P〈0.001）;而Bax的表达正好相反,去势组大鼠胸腺组织中Bax表达量明显低于假手术组（P〈0.001）,给予丙酸睾酮后Bax表达量明显增加（P〈0.001）;结论丙酸睾酮可诱导大鼠胸腺细胞凋亡,并抑制大鼠胸腺组织中Bcl-2的表达,促进Bax的表达。     

HeLa及子宫颈癌组织中的DR5和bcl-2表达及其相关性

目的探讨死亡受体DR5、bcl-2蛋白在HeLa细胞株和宫颈癌组织中表达及其相关性。方法采用流式细胞术检测HeLa细胞株细胞表面DR5表达,免疫组化法检测DR5和bcl-2蛋白在HeLa细胞株的表达情况及在76例宫颈癌(包括鳞癌50份,腺癌26份),30例宫颈上皮肉瘤变(CIN)和20例正常宫颈组织中表达,并分析两者的相关性。结果 HeLa细胞株细胞表面DR5表达率30%;DR5和bcl-2蛋白主要在CIN和宫颈癌细胞质表达,DR5蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中阳性表达率分别是66%、62%、40%和35%。鳞癌组织DR5表达高于腺癌,但无统计学意义(P>0.05);宫颈癌组织中DR5的表达量显著强于CIN和正常宫颈组织,差异均有统计学意义(P<0.05),CIN与正常宫颈组织比较,差异无统计学意义(P>0.05)。bcl-2蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织的阳性表达率分别为70%、65%、50%和20%。DR5和bcl-2蛋白在宫颈癌组织中的表达呈正相关(χ2=10.75,P=0.000)。结论 DR5和bcl-2蛋白在宫颈癌组织中的表达呈正相关,DR5蛋白表达可能与宫颈癌的发生、发展有一定的关系。     

Expression of steroid hormone receptors, their regulated proteins, and bcl-2 protein in myofibroblastoma of the breast

AIMS: To investigate the possible role of steroid hormones in the pathogenesis of myofibroblastoma (MFB) of the breast, we analysed the immunohistochemical expression of oestrogen, progesterone, androgen receptors, their regulated proteins and bcl-2 protein in a series of this rare tumour. METHODS AND RESULTS: Paraffin-embedded sections from seven cases of MFB of the breast (five male; two female) were immunohistochemically tested for the expression of oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), oestrogen-regulated pS2 protein, androgen-regulated prostate-specific antigen (PSA) and bcl-2 protein. Rare cases of benign spindle cell tumours or tumour-like lesions of the breast (primitive fibromatosis, inflammatory pseudotumour, muscular hamartoma) which enter into the differential diagnosis with MFB, were also investigated and compared with MFB. All cases of MFB showed a diffuse (70-90% of neoplastic cells) and strong nuclear labelling with ER and PR, whereas AR was expressed only in three cases (two men and one woman) in about 60-70% of cells. Conversely, no immunostaining was detected for the pS2 protein and PSA. bcl-2 protein immunoreactivity was found in all cases of MFB, although with a variable degree of expression. No expression for steroid hormone receptors, their regulated-proteins and bcl-2 protein was observed in the rare benign spindle cell lesions of the breast included in this study. CONCLUSION: The in-situ detection of ER, PR and AR suggests that steroid hormones and their receptors are implicated in the pathogenesis of breast MFB. The consistent demonstration of bcl-2 protein, associated with a positive ER/PR status, provides evidence that bcl-2 may be an oestrogen-regulated protein also in MFB and that probably plays a role in the tumorigenesis. Finally, we postulate that the ER/PR and bcl-2 positive immunoprofile of MFB of the breast, in contrast to the negative profile of other rare primitive benign spindle cell lesions of the breast herein studied, might be exploited as an ancillary diagnostic aid in differential diagnosis of doubtful cases.