Survivin在非小细胞肺癌细胞胞质和胞核的不同表达及其预后意义

[目的]探讨非小细胞肺癌（NSCLC）中survivin胞质和胞核的不同表达与临床病理特征及预后的关系．[方法]将有完整临床与生存资料的92例NSCLC及10例正常肺组织标本制作成组织芯片,应用免疫组织化学SP法检测sunivin的表达。[结果]肺癌组织中survivin胞质和胞核阳性表达率分别为87．0％和70．7％．正常肺组织均为阴性（P〈0．001）。Sunrvivin胞质和胞核阳性表达与年龄、性别、吸烟、病理类型、分化程度和肿瘤大小均无关（P〉0．05）,而survivin胞质阳性表达在淋巴结阳性者中升高（P=0．029）、生存分析显示surivin胞质和胞核表达均与生存期无关（P〉0．05）分层分析表明,鳞癌病人中survivin胞核阴性者生存较长．而在腺癌病人中survivin胞核阳性者生存更好（P=0．073）。多因素分析显示survivin表达不是影响预后的独立危险因素、[结论]NSCLC患者survivin表达明显升高,检测其表达可能有助于诊断,survivin胞核的不同表达可能在预后判定巾有一定作用.     

非小细胞肺癌中EGFR、VEGF和COX-2表达的预后意义

目的：探讨EGFR、VEGF和COX-2这三种与肿瘤血管生成相关的蛋白在非小细胞肺癌（NSCLC）中的表达与临床病理特征和预后的关系。方法：将88例NSCLC及10例正常肺组织标本制作成组织芯片，应用免疫组化S—P法检测EGFR、VEGF和COX-2的表达，并与临床病理特征及预后进行比较分析。结果：EG-FR、VEGF和COX-2在NSCLC标本中的阳性表达率分别为46．6％、67．0％和71．6％，而三者在10例正常肺组织中表达均为阴性。EGFR表达与各种临床病理参数均无关（P〉0．05），VEGF在女性病人中表达升高（P=0．035），COX-2在女性、不吸烟者、腺癌和淋巴结转移阳性者中表达升高（P值分别为0．005，0．027，0．001和0．003）。EGFR和VEGF、VEGF和COX-2之间呈正相关关系（γ=0．267，P=0．012和γ=0．416，P=0．000），而EGFR和COX-2之间无相关性（P=0．441）。生存分析显示EGFR和VEGF表达与生存期无关（P=0．110和P=0．773），而COX-2阳性表达者生存期短（P=0．014）。多因素分析显示EGFR、VEGF和COX-2表达不是影响预后的独立危险因素。结论：EGFR、VEGF和COX-2在NSCLC中表达升高且存在正相关关系，可能在肿瘤血管形成过程中起协同作用。COX-2阳性表达者生存期短，可能在预后判定中有重要作用。     

survivin和COX-2在非小细胞肺癌中的表达及意义

背景与目的 应用组织芯片技术可以方便快捷地进行免疫组化染色。本研究的目的是探讨survivin和COX-2与非小细胞肺癌（NSCLC）患者临床病理特征和长期预后之间的关系。方法 将88例NSCLC及5例正常肺组织标本制作成组织芯片，应用免疫组织化学SP法检测survivin和COX-2的表达。结果 survivin胞质和胞核阳性表达率分别为94．3％和79．5％，COX-2阳性表达率为71.6％，而正常肺组织均为阴性，NSCLC中的survivin和COX-2表达明显高于正常肺组织（P〈0．005）。survivin胞核阳性表达率在吸烟者中明显升高（P=0．002）。COX-2在女性、不吸烟者、腺癌和淋巴结转移阳性者中表达明显升高（P〈0．05）。单因素分析显示COX-2表达与患者生存有密切关系（P=0．014），而survivin表达与生存未见明显关系。多因素分析显示survivin和COX-2均不是影响预后的独立危险因素。结论 survivin检测可能有助于NSCLC的诊断；COX-2阳性表达者预后差，可能在预后判定中有重要作用。     

非小细胞肺癌中Bcl-2和COX-2表达的预后意义

目的探讨Bcl-2和COX-2表达与非小细胞肺癌(non-smallcelllungcanc-er,NSCLC)预后的关系。方法将88例NSCLC及10例正常肺组织标本制作成组织芯片,应用免疫组织化学SP法检测Bcl-2和COX-2的表达,并与临床病理特征及长期生存进行比较分析。结果Bcl-2胞质和胞核阳性表达率分别为54.5%和42.0%,COX-2胞质阳性表达率为71.6%,而正常肺组织均为阴性,NSCLC患者的Bcl-2胞质和胞核表达和COX-2表达明显高于正常肺组织,P值分别为0.001、0.012和0.000。Bcl-2胞质表达在男性、吸烟者、鳞癌、无淋巴结转移者中表达升高,P值分别为0.001、0.000、0.000和0.002,而与年龄、分化程度和肿瘤大小无关。Bcl-2胞核表达在女性、不吸烟者、腺癌和肿瘤大小为T3和T4者中表达升高,P值分别为0.001、0.006、0.000和0.025,而与年龄、分化程度和淋巴结是否转移无关。COX-2在女性、不吸烟者、腺癌和淋巴结转移阳性者中表达升高,P值分别为0.005、0.027、0.001和0.003,与年龄、分化程度和肿瘤大小无关。Bcl-2胞质表达的患者生存时间更长,而Bcl-2胞核表达的患者生存时间更短。COX-2表达者生存时间短。多因素分析显示,Bcl-2和COX-2不是影响NSCLC预后的独立危险因素。结论NSCLC患者中Bcl-2胞质和胞核表达可能具有相反的预后意义,Bcl-2胞质表达者预后好,而Bcl-2胞核表达者预后差,COX-2阳性表达者预后差,两者联合检测可能在NSCLC预后判定中有重要作用。     

非小细胞肺癌HGF和ECE的表达及其与淋巴结转移和预后的关系

目的：研究HGF与ECE蛋白在非小细胞肺癌（NSCLC）组织中表达的临床意义。方法：用免疫组织化学方法检测77例NSCLC组织中HGF与ECE的表达，分析其与吸烟史、肿瘤的大小、癌的组织学类型、组织分化程度、淋巴结转移和预后的关系。结果：77例NSCLC组织中HGF与ECE的阳性率分别为44％和45％。HGF与ECE的表达与淋巴结转移呈正相关（P分别为0．003和0．001，r分别为0．339和0．467），与临床分期、手术后生存期呈负相关（P〈0．05）。NSCLC组织中HGF和ECE的表达呈正相关（P=0．000，r=0．501）。HGF与ECE的表达与患者吸烟、肿瘤大小、癌组织学类型和组织分化程度无关（P〉0．05）。结论：HGF与ECE蛋白的表达与NSCLC的淋巴结转移和预后密切相关，它的高表达提示非小细胞肺癌患者预后不良。     

利用组织微阵列研究RASSF1A和Survivin基因在非小细胞肺癌中的表达

目的探讨RASSF1A和Survivin基因的蛋白表达与非小细胞肺癌（NSCLC）临床病理特征的关系及其临床意义。方法免疫组织化学法检测RASSF1A和Survivin在NSCLC组织微阵列中的蛋白表达。结果RASSF1A蛋白在NSCLC中的阳性率（46．8％〉显著低于正常肺组织（92．9％）（P〈0．001），但Survivin阳性率（75．8％）显著高于正常肺组织（0）（P〈0．001）；RASSF1A蛋白在临床Ⅰ期和Ⅱ期NSCLC中分别显著高于临床Ⅲ期（P〈0．001，P〈0．001），Survivin在临床I期和临床Ⅱ期NSCLC中的阳性率显著低于临床Ⅲ期者（P=0．003，P=0．001），淋巴结转移性NSCLC的RASSF1A阳性率显著低于无淋巴结转移者（P〈0．05）；RASSF1sA和Survivin蛋白在NSCLC中的表达呈负相关（r=-0．780，P〈0．001）。结论RASSFlA蛋白表达下调、Survivin蛋白高表达及其两者的表达失平衡在NSCLC的发生、发展中可能具有重要作用，RASSF1和Survivin有望成为评估肺癌淋巴结转移和预后预测的重要分子标志。     

COX-2和Survivin在食管癌组织芯片的表达及临床意义

目的：检测食管癌组织中COX-2和Survivin蛋白的表达情况及其与食管癌患者临床病理特征的关系。方法：采用免疫组化EnVision法和组织芯片技术，检测手术切除的56例食管癌患者肿瘤组织中COX-2和Survivin蛋白的表达状况，分析其与临床病理特征之间的关系及COX-2和Survivin表达的相关性。结果：COX-2在食管癌组织表达主要分布于细胞质，少数位于细胞膜，而Survivin则分布于细胞核。COX-2和Survivin在食管癌组织阳性表达率分别为69．6％和71．4％，而在食管癌旁组织则无表达。COX-2表达与性别（P=0．543）、年龄（P=0．561）和肿瘤分化程度（P=0．216）尤关，但与肿瘤浸润深度（P=0．046）、淋巴结转移（P=0．001）及TNM分期（P=0．001）密切相关。Survivin表达与性别（P=1．000）、年龄（P=1．000）和肿瘤分化程度（P=0．333）亦无关，与肿瘤浸润深度（P=0．020）、淋巴结转移（P=0．003）及TNM分期（P=0．002）具有相关性。COX-2和Survivin均为阳性表达35例（62．5％），呈正相关（P=0．000，r=0．614）。结论：COX-2和Survivin在食管癌中呈过度表达，并与肿瘤浸润深度、淋巴结转移和临床分期密切相关，两者表达呈正相关，提示COX-2和Survivin在肿瘤进展中可能有协同作用。     

Bcl-2、Bax在乳腺癌中的表达及其与预后的关系

目的检测浸润性乳腺癌组织中Bcl-2及Bax的表达，探讨乳腺癌的发生发展过程中凋亡调控因子的作用，进一步明确这些指标与乳腺癌的临床病理和预后的关系，并与乳腺癌常用的检测指标ER、PR进行比较分析，为乳腺癌的临床治疗和预后判断提供更好的理论依据。方法用免疫组化方法检测60例手术切除的乳腺癌组织中Bcl-2、Bax、ER及PR的表达，研究其与临床病理特征的关系以及对预后的影响。结果①乳腺癌组织中Bcl-2及Bax的阳性表达率分别为51．7％、55．0％。②Bcl-2与组织学分级呈显著负相关（x^2=9．6774，P=0．0097），与淋巴结转移呈负相关（，=4．423l，P=0．0355）。而且在转移淋巴结个数为l～3个和〉／4个之间Bcl-2的表达有差异（x^2=5．1074，P=0．0238）．③随着组织学分级的提高，Bax的阳性表达率逐渐增高，各组间差异显著（P=0．0149）；淋巴结转移组癌组织中Bax的阳性表达率明显高于无淋巴结转移组（P=0．0446）。④Bax阴性表达病人的生存期明显长于阳性表达病人（p=0.0063，P=0．0009），而Bcl-2的阳性表达病人的生存期却明显长于阴性表达病人（P=0．0049），Bcl-2／Bax〉1组病人的生存期优于Bcl-2／Bax≤1组（B=0．0488）。③Bcl-2与Bax呈负相关，Bel-2与ER、PR呈正相关，Bcl-2／Bax比值与Eli呈正相关，Bax与Eli、PR之间均不具有相关性。结论Bcl-2的高表达与分化程度较低、无淋巴结转移或转移个数少以及较长的生存期有关，与Eli、PR呈明显正相关，是预后好的因素之一。Bax的表达与组织学分级、淋巴结转移以及预后呈负相关，Bax的高表达促进了乳腺癌的发生发展。乳腺癌组织中Bcl-2基因的高表达及Bax基因的低表达使Bcl-2／Bax比值高者恶性程度低，淋巴结转移少，ER的阳性率高，生存期长，低凋亡易感性与好的生物学行为和预后有关。bcl-2与bax呈明显负相关，bcl-2、bax共同作用，在乳腺癌的发生、发展及预后中起一定作用。     

食管癌组织Survivin表达及其与Bcl-2表达相关性研究

目的：研究Survivin在食管癌发生、发展中的作用及其与预后、Bcl-2表达的关系。方法：应用免疫组化SP法检测Survivin和Bcl-2在30例正常食管黏膜组织、106例食管癌组织中的表达。结果：Survivin在食管癌组织中的阳性表达显著高于正常食管黏膜组织，P=0．000；食管癌浸润浆膜层组的Survivin阳性表达明显高于浸润肌层组，P=0．013；食管癌伴淋巴结转移组的Survivin阳性率显著高于无淋巴结转移组，P=0．011；Bcl-2阳性组的Survivin阳性表达明显高于Bcl-2阴性组，P=0．000；Survivin阴性表达的食管癌病例术后5年生存率显著高于Survivin阳性表达的食管癌病例，P=0．043。结论：Survivin可作为食管癌的诊断标志，检测食管癌组织中Survivin的表达可作为判断食管癌转移及预后的参考指标。在食管癌组织中Survivin的表达与Bcl-2的表达密切相关，Survivin和Bcl-2在食管癌的发生、发展过程中起协调作用。     

非小细胞肺癌组织中SSTR2A和SSTR5的表达及其临床意义

目的：探讨生长抑素（somatostatin，SST）亚型SSTR2A和SSTR5蛋白在非小细胞肺癌（non-small cell lung cancer，NSCLC）组织中的异常表达及其意义。方法：SP法检测SSTR2A和SSTR5蛋白在62例NSCLC组织和10例癌旁正常肺组织中的表达情况，并进行预后随访。结果：在62例NSCLC组织中，SSTR2A有30例（48．4％）表达阳性；ssTR5有44例（71．0％）表达阳性。SSTR2A、SSTR5蛋白表达与NSCLC的TNM分期密切相关，P=0．014；但与NSCLC患者的年龄、性别、吸烟与否、病理类型和肿瘤大小均无明显相关，P〉0．05。SSTR2A、SSTR5蛋白阳性表达者的3年生存率分别为64．52％和65．91％，阴性表达者为45．16％和22．22％，两者之间差异有统计学意义，P〈0．05。结论：SSTR2A、SSTR5蛋白表达提示NSCLC预后好．生存期长；且与癌恶变程度相关，有可能作为判断NSCLC预后的指标。     

Survivin、P53、Bcl-2蛋白与非小细胞肺癌临床病理因素的关系

目的探讨survivin、p53、Bcl-2蛋白在非小细胞肺癌(NSCLC)中的表达及与临床病理因素的关系。方法应用免疫组织化学法(SP)检测80例NSCLC肿瘤组织、20例肺良性病变组织中survivin、p53、Bcl-2蛋白表达情况。结果survivin、p53、Bcl-2蛋白在肺癌组织中的阳性表达率分别为61.3%(49/80)、55.0%(44/80)和50.0%(40/80),高于肺良性病变组织中的表达水平(P<0.05)。survivin蛋白的表达在不同的TNM分期之间有显著性差异,但与肺癌组织的细胞类型、分化程度及淋巴结转移无明显关系;P53蛋白的表达在不同的淋巴结转移情况之间以及在不同的TNM分期之间有显著性差异;Bcl-2蛋白的表达在不同的细胞类型之间有显著性差异(P<0.05)。肺癌组织中p53,Bcl-2蛋白与survivin蛋白表达显著相关(P<0.05)。结论survivin、P53、Bcl-2蛋白与肺癌的发生和发展密切相关,并可能起协同作用,其综合检测对肺癌的病情判断和预后评价具有一定价值。     

Nuclear survivin predicts recurrence and poor survival in patients with resected nonsmall cell lung carcinoma

BACKGROUND: Survivin, which is a member of the inhibitor of apoptosis protein gene family, regulates both programmed cell death and mitosis. It has been shown that survivin expression and its subcellular localization both have prognostic value for patients with malignant disease. In this study, the authors investigated whether nuclear or cytoplasmic staining of survivin was a prognostic marker for patients with lung carcinoma. METHODS: Paraffin-embedded tissue blocks from 144 patients with Stage I and II resected nonsmall cell lung carcinoma (NSCLC) were obtained for immunohistochemical staining. Three specimens from each patient were prepared and stained with a survivin-specific antibody. Nuclear and cytoplasmic staining was graded from 1 to 3 based on intensity. RESULTS: Patients who had nuclear staining for survivin had a significantly increased risk of disease recurrence (hazard ratio, 2.95; P = 0.0046) and death (hazard ratio, 2.74; P = 0.0086). CONCLUSIONS: The nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with resected Stage I and II NSCLC.     

Survivin、p53、Bcl-2蛋白在非小细胞肺癌中的表达及意义

目的:探讨Survivin基因在非小细胞肺癌(NSCLC)中的表达,以及与P53,Bcl-2蛋白表达的相互关系。方法:应用免疫组织化学法(SP)检测80例NSCLC肿瘤组织、20例肺良性病变组织中Survivin蛋白、P53蛋白、Bcl-2蛋白表达情况,并将结果进行了相关分析。结果:Survivin蛋白在肺良性病变组织中不表达,在61.3%(49/80)的NSCLC组织中有表达,且Survivin的表达与肺癌患者的TNM分期有关,但与肺癌的细胞类型、分化程度及淋巴结转移无明显关系;肺癌组织p53蛋白阳性表达率55.0%(44/80),与肺癌的TNM分期及淋巴结转移有关,肺良性病变组织中无p53蛋白表达;肺癌组织Bcl-2蛋白阳性表达率50.0%(40/80)明显高于肺良性病变组织的10.0%(2/20),其中鳞癌组织的表达率62.2%,明显高于腺癌组织的表达率34.3%(P<0.05);肺癌组织中P53,Bcl-2蛋白与Survivin蛋白表达显著相关(P<0.05)。结论:Survivin蛋白在肺癌组织中表达上调,提示该基因对NSCLC的发生发展起重要作用。Survivin基因有望成为肺癌基因治疗的新靶点;Survivin蛋白表达与肺癌的TNM分期密切相关,提示可作为判断病情和评价预后的指标。Sur vivin蛋白的表达与p53蛋白、Bcl-2蛋白的表达均呈正相关,三者在肺癌的发生中可能起协同作用。     

The role of survivin on overall survival of non-small cell lung cancer, a meta-analysis of published literatures

The prognostic value of survivin for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. The authors performed a meta-analysis of the literatures in order to clarify its impact. Published studies were identified using an electronic search in order to aggregate the available survival results. To be eligible, a study had to have dealt with survivin assessment in NSCLC patients on the primary site and have analyzed survival according to survivin expression. There were 10 eligible studies and data from eight studies where non-location specific immunohistochemistry (IHC) definition system, in situ hybridization (ISH) and RT-PCR used were combined to present the impact of survivin on overall survival (OS) of NSCLC. The level of survivin expression correlated with the OS of NSCLC patients significant (RR 1.88, 95% CI 1.31-2.70, P=0.0006). Data of seven studies were combined to demonstrate that the level of survivin correlated with the OS of NSCLC patients who had received radical surgeries (RR 1.79, 95% CI 1.45-2.20, P<0.00001). Data from three studies were combined to find that the level of nuclear survivin did not have impact on OS of NSCLC patients (RR 1.58, 95% CI 0.87-2.85, P=0.13). Positive-survivin expression might be a prognostic factor for NSCLC patients, nuclear survivin positivity could not work as a prognostic factor for NSCLC patients based on current clinical data. Larger clinical trails with widely accepted assessment methods are necessary to define the precise prognostic significance for survivin in NSCLC patients.     

Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer.

PURPOSE: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. EXPERIMENTAL DESIGN: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. RESULTS: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmic-to-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of OS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). CONCLUSION: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor.     

Nuclear survivin as a biomarker for non-small-cell lung cancer

Survivin inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localisation of survivin predicts survival of 48 patients with resected non-small-cell lung cancer (NSCLC). Patients with nuclear staining of survivin had significantly worse survival (relative risk: 3.9, P=0.02). Therefore, survivin may be a biomarker for NSCLC.     

Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma

Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.     

Does immunointensity account for the differences in prognostic significance of Bcl-2 expression in non-small cell lung cancer?

Bcl-2 is an oncogenic protein that plays a central role in apoptosis. The association of Bcl-2 expression and prognosis in non-small cell lung cancer (NSCLC) is unclear, with some studies showing improved outcome whilst others show no survival advantage. We evaluated 178 surgically resected NSCLC specimens for Bcl-2 and p53 immunoexpression. Bcl-2 staining was present in 34.9% of cases (weakly staining 24.2%, strongly staining 10.7%), nuclear p53 in 43. 3% and cytoplasmic p53 in 10.7%. There was no association between p53 and survival. Bcl-2 immunoexpression correlated with improved outcome (p=0.04). A sub-group of strongly Bcl-2 staining cases had a poor survival compared to those that stained weakly (p=0.01). The strongly staining cases had a similar survival to negative cases. Immunointensity may therefore account for the disparity in results regarding the prognostic significance of Bcl-2 demonstrated in previous studies.