胃腺癌中β-连环蛋白、c-myc表达及其临床意义

目的研究胃腺癌和癌旁组织中β-连环蛋白和c-myc的表达及其临床意义。方法收集102例胃腺癌患者的手术切除标本共297份，其中取自癌组织102份，癌旁组织195份（肿瘤边缘2cm以内97份，5cm以外98份）。将标本分别制成282点、156点和156点三块组织芯片，采用免疫组织化学法检测胃组织芯片中β-连环蛋白和c-myc的表达。结果β-连环蛋白和c-myc基因表达在胃黏膜癌变过程中呈上升趋势，从肠上皮化生开始即有明显增高，在胃癌显著高于肠上皮化生（P〈0．05，P〈0．001）。肛连环蛋白的异常表达与胃腺癌的分化程度及浸润深度有关（P〈0．05），c-myc表达与胃腺癌的分化程度有关（P〈0．05）。胃腺癌中β-连环蛋白和c-myc表达呈明显正相关（P〈0．05）。结论β-连环蛋白异常表达可能激活靶基因c-myc的表达，并在胃腺癌发生发展中起重要作用。     

RCAS1、Caspase-8在胃腺癌组织中的表达及意义

目的探讨RCAS1、Caspase-8在胃腺癌组织中的表达及其意义。方法采用免疫组化SP法检测46例胃腺癌组织及其切端正常胃黏膜组织中RCAS1、Caspase-8的蛋白表达。结果正常胃黏膜组织及胃腺癌组织中RCAS1蛋白的阳性表达率分别为60.87%（28/46）和84.78%（39/46）（P〈0.05）。正常胃黏膜组织及胃腺癌组织中Caspase-8蛋白的阳性表达率分别为80.43%（37/46）和65.22%（30/46）（P〈0.05）。二者在胃癌组织中的表达呈负相关性（r=-0.321、P〈0.05）。结论 RCAS1、Caspase-8蛋白在胃腺癌组织中的异常表达与胃腺癌的发生、发展有关。     

胃腺癌组织中Snail、E-cadherin蛋白的表达变化及意义

目的观察胃腺癌组织中Snail、E-cadherin蛋白的表达变化,并探讨其意义。方法采用免疫组化SP法检测112例胃腺癌患者肿瘤组织和79例癌旁组织中的Snail、E-cadherin蛋白。结果胃腺癌组织中Snail阳性92例（82.1%）,E-cadherin阳性38例（33.9%）,癌旁组织中分别为28例（35.4%）、79例（100%）,胃腺癌组织中Snail、E-cadherin蛋白阳性表达率相比P均〈0.05。胃腺癌组织中Snail的表达与肿瘤浸润深度、分化类型、是否有淋巴结转移以及远处转移相关（P均〈0.05）。E-cadherin的表达与肿瘤浸润深度、分化类型、是否有淋巴结转移、远处转移以及临床分期相关（P均〈0.05）。Snail蛋白和E-cadherin蛋白在胃腺癌组织中的表达呈明显负相关（r=-0.212,P〈0.05）。结论胃腺癌组织中Snail蛋白表达上调,E-cadherin蛋白表达下调。联合检测Snail、E-cadherin蛋白可以作为预测胃癌恶性程度的指标     

胃癌组织中Cyclin E、p57与CDC25A的表达及意义

采用免疫组化SP法检测30例进展期胃癌组织、癌旁组织和10例正常胃组织中Cyclin E、p57与双重特异性磷酸酶A（CDC25A）的表达。结果在胃癌组织、癌旁组织和正常胃组织标本中p57的阳性表达率分别为40%（12/30）、73.3%（22/30）、90.0%（9/10）;Cyclin E的阳性表达率分别为70%（21/30）、36.7%（11/30）、10.0%（1/10）;CDC25A的阳性表达率分别为73.3%（22/30）、43.3%（13/30）、20.0%（2/10）。Cyclin E与CDC25A的表达呈正相关（r=0.371,P〈0.05）,p57与CDC25A的表达呈负相关（r=-0.412,P〈0.05）,p57与Cyclin E的表达呈负相关（r=-0.384,P〈0.05）。     

RECK,MMP-9及TGF-β1在胃癌组织中的表达及其相互关系

目的研究RECK,MMP-9和TGF-β1在胃癌及正常胃组织中的表达,探讨其在胃癌的发生、发展、浸润和转移中的作用.方法选择临床及病理资料齐全的存档胃腺癌蜡块标本54例,另取正常胃黏膜标本15例作对照.采用第二代通用型二步法监测系统(PV-9000)免疫组化方法检测RECK,MMP-9及TGF-β1在胃癌及正常胃组织中的表达.结果RECK在胃癌组织中低表达(51.9%),并随肿瘤浸润深度的加深、淋巴转移的产生、远隔转移的发生、临床分期的提高、肿瘤病理分化程度的降低而降低(P＜0.05).MMP-9在胃癌组织中高表达(75.9%),并随肿瘤浸润深度的加深、淋巴转移的产生、临床分期的提高、肿瘤病理分化程度的降低而增高(P＜0.05).TGF-β1在胃癌组织中高表达(77.8%),并随淋巴转移的产生、临床分期的提高、肿瘤病理分化程度的降低而增高(P＜0.05).胃癌组织中RECK与MMP-9、TGF-β1的表达呈负相关(r=-0.618,P＜0.001;r=-0.620,P＜0.001),MMP-9与TGF-β1的表达呈正相关(r=0.716,P＜0.001).结论胃癌组织中RECK低表达,MMP-9,TGF-β1高表达.RECK,MMP-9及TGF-β1可以作为评估胃癌发生浸润转移的重要指标.     

胃癌组织中CD_（44） V6、E-钙黏附素的表达变化及意义

目的观察胃癌组织中CD44V6、E-钙黏附素（E-cadherin）的表达变化,并探讨其临床意义。方法采用免疫组化法检测198例胃癌组织、50例正常胃组织中的CD44V6、E-cadherin,以单克隆抗体细胞角蛋白（AE1/AE3）作为标记采用免疫组化方法判断胃癌淋巴结微转移。结果胃癌组织中CD44V6、E-cadherin的阳性率分别为78.79%、55.05%,正常胃黏膜组织中分别为0、100%,两者相比,P均〈0.05;CD44V6表达与胃癌生长方式、浸润程度及TNM分期有关（P均〈0.05）;E-cadherin表达与胃癌分化程度、浸润程度及TNM分期有关（P均〈0.05）,二者的表达呈负相关（r=-0.462,P〈0.01）。胃癌患者中,淋巴结转移108例,淋巴结微转移64例。CD44V6表达与淋巴结转移呈正相关（r=0.573,P〈0.05）,而与淋巴结微转移呈负相关（r=-0.329,P〈0.05）。E-cadherin与淋巴结转移及微转移均呈负相关（r分别为-0.496、-0.407,P均〈0.05）。结论胃癌组织中CD44V6、E-cadherin的表达增高,二者在胃癌的浸润转移过程中发挥重要作用。     

Nodal蛋白在胃腺癌组织中的表达及意义

目的探讨Nodal蛋白在胃腺癌组织中的表达情况及其与临床病理特征和生存期的关系。方法选择50例胃腺癌患者,随访生存期;取手术切除标本行免疫组织化学检测Nodal蛋白表达,标准评定采用半定量法。结果 50例胃腺癌组织中,46例Nodal阳性表达,阳性表达率为92.0%;Nodal蛋白表达与胃癌组织分化程度无相关性（P〉0.05）,与肿瘤是否发生血管浸润和淋巴结转移呈正相关（P〈0.05）。Nodal蛋白表达≤25%组与表达〉26%组比较,术后生存期存在统计学差异（P〈0.05）。结论 Nodal蛋白在胃癌组织中高表达,胃癌组织中Nodal蛋白表达水平可作为评价生存期预后的有价值指标。     

Paxillin、FAK和PTEN在胃腺癌组织中的表达及其临床意义

背景：研究表明Paxillin、黏着斑激酶（FAK）和PTEN在许多肿瘤的发生、发展、侵袭、转移中发挥重要作用,但联合检测三者在胃癌中表达的报道罕见。目的：研究正常胃黏膜和胃腺癌组织中Paxillin、FAK和PTEN的表达及其临床意义。方法：以免疫组化SP法分别检测40例正常胃黏膜组织和88例胃腺癌组织中Paxillin、FAK和PTEN表达,并分析其与胃腺癌临床病理特征的关系以及Paxillin与PTEN表达之间的相关性。结果：与正常胃黏膜组织相比,胃腺癌组织Paxillin（65．9％对32．5％,P〈0．05）、FAK（56．8％对17．5％,P〈0．05）阳性表达率显著增高,PTEN阳性表达率显著降低（47．7％对100％,P〈0．05）。Paxillin、FAK和PTEN表达与胃腺癌分化程度、浸润深度、淋巴结转移和TNM分期有关（P〈0．05）．与性别和年龄无关。胃腺癌组织中Paxillin表达与PTEN表达呈显著负相关（r=-0．369,P〈0．05）。结论：Paxillin、FAK高表达和PTEN低表达可能与胃腺癌的浸润、淋巴结转移等恶性生物学行为相关,联合检测三者可能有助于判断胃腺癌恶性程度和患者预后。     

萎缩性胃炎及胃癌中垂体肿瘤转化基因和c-myc蛋白的表达及其二者的相关性

目的研究垂体肿瘤转化基因（PTTG）基因和c-myc蛋白在胃癌发生发展中的作用及二者的相关性。方法采用免疫组织化学SP法检测90例正常胃组织、慢性萎缩性胃炎及胃癌组织中PTTG基因和c-myc蛋白的表达。结果PTTG基因和c-myc蛋白在正常胃组织中表达均为阴性，在慢性萎缩性胃炎、胃癌组织中表达明显高于正常胃组织（P〈0．05），二者的表达强度在慢性萎缩性胃炎组与胃癌组间比较均有显著性差异（P〈0．05）。二者的表达均与胃癌的病理组织学分级、临床分期及淋巴结转移有关（P〈0．05），而与组织学类型无关（P〉0．05）。PTTG基因和c-myc蛋白表达强度呈显著正相关（P〈0．05）。结论PTTG基因和c-myc蛋白在胃癌的发生发展中有协同作用，可作为反映胃癌生物学行为的指标。     

Claudin-1、Claudin-3在胃癌组织中的表达及意义

应用免疫组织化学pv-9000（两步法）检测胃癌组织及健康胃组织中Claudin-1、Claudin-3的表达。结果与健康胃组织比较,胃癌组织中Claudin-1的表达降低,Claudin-3的表达升高;Claudin-1、Claudin-3在胃癌中的表达呈负相关（r=0.330,P〈0.05）。提示Claudin-1、Claudin-3的检测对于胃癌预后的评估有重要价值。     

Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.METHODS:Purified gastric adenocarcinoma cells(GAC)and normal gastric epithelial cells(NGEC)were obtained from 15 patients with gastric cancer by laser capture microdissection.All of the peptide specimens were labeled as18O/16O after trypsin digestion.Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry(nanoRPLC-MS/MS).The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis.The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry(IHC).The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.RESULTS:A total of 78 differential proteins were identified.Western blotting revealed that ANXA1 expression was significantly upregulated in GAC(2.17/1,P<0.01).IHC results showed the correlations between ANXA1protein expression and the clinicopathological parameters,including invasive depth(T stage),lymph node metastasis(N stage),distant metastasis(M stage)and tumour-lymph node metastasis stage(P<0.01).However,the correlations between ANXA1 protein expression and the remaining clinicopathological parameters,including sex,age,histological differentiation and the size of tumour were not found(P>0.05).CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis,progression,invasion and metastasis of GAC.This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.     

Bcl-2、Bax、P21-WAF1、P16-MTS1蛋白在胃腺癌演化系列中的表达

目的　通过对胃腺癌演化系列胃粘膜中Bcl 2、Bax、P2 1 WAF1、P16 MTS1蛋白的检测 ,探讨胃腺癌发生的机制及四种蛋白表达与胃腺癌生物学行为的关系。方法　 1、利用免疫组化S P法检测胃癌演化系列胃粘膜中Bcl 2、Bax、P2 1 WAF1、P16 MTS1蛋白的表达 ;2、利用SPSS统计软件包作统计学分析处理。结果　在CSG、CAG、IM系列胃粘膜中Bax、Bcl 2表达先高后低 ,而P16 MTS1、P2 1 WAF1表达先低后高 ,(P <0 .0 5 )。高分化胃腺癌中Bcl 2、Bax、P2 1 WAF1、P16 MTS1表达较低分化者高 ;P16 MTS1表达在非贲门癌中比贲门癌中高 ,P2 1 WAF1表达在有淋巴结转移的胃腺癌中较低 (P<0 .0 5 )。结论　Bax、Bcl 2的高表达及P2 1 WAF1、P16 MTS1的表达受抑可能参与胃腺癌发生 ;四种蛋白异常表达均与胃腺癌分化呈正相关 ;P16 MTS1、P2 1 WAF1的表达异常与胃腺癌的发生部位及淋巴结转移相关。     

ANXA2和ANXA4在胃腺癌中的表达及临床意义

目的:研究膜联蛋白A2(AnnexinA2,ANXA2)、膜联蛋白A4(AnnexinA4,ANXA4)在人体胃腺癌(gastric adenocarcinoma cells,GAC)的表达,探讨其表达与GAC生物学行为的关系及两种蛋白的相关性.方法:免疫组织化学SP法检测组织芯片中75对配对的GAC和其相应癌旁组织ANXA2和ANXA4的表达.结果:在GAC和癌旁组织中ANXA2、ANXA4的表达分别为:33.1%(25)vs1.3%(1)、68.0%(51)vs25.5%(13),二者在GAC的表达显著高于癌旁组织(x2=24.448,P=0.000;x2=39.353,P=0.000);ANXA2和ANXA4在GAC表达呈正相关(r=0.335,P=0.003);两种蛋白的表达与GAC的浸润深度、淋巴结转移、TNM分期和分化程度有关(P<0.05),与年龄、性别和远处转移无关(P>0.05);肿瘤大小与ANXA2表达有关(P<0.01),与ANXA4表达无关(P>0.05).结论:ANXA2和ANXA4的表达上调可能共同参与了GAC的发生、发展、浸润和转移,可作为临床预测GAC预后的标志物和治疗靶点.     

胃癌组织中Raf激酶抑制蛋白的表达临床意义

目的 探讨Raf激酶抑制蛋白(RKIP)在胃癌中的差异表达及临床意义.方法 采用激光捕获显微切割技术(LCM)获得12例纯化的胃腺癌细胞(GAC)及其癌旁(＞5 cm)胃黏膜上皮细胞(NGEC),应用18O/16O分别标记两种细胞样本酶切后的多肽混合物.结合纳升级液相色谱定量鉴定GAC和NGEC的差异表达蛋白质.免疫印迹法验证差异蛋白RKIP在胃癌中的表达.免疫组化检测RKIP蛋白在胃癌组织(118例)、癌旁胃黏膜组织(70例)、转移的淋巴结组织(35例)的表达.结果 共筛选出78个差异表达蛋白质,其中RKIP蛋白表达水平在GAC中较NGEC明显下调(1:4.37).免疫组化结果显示,RKIP蛋白表达与胃癌的浸润深度、TNM分期及淋巴结转移呈负相关,与分化程度呈正相关(P＜0.05).结论 胃癌组织中RKIP蛋白低表达可能影响胃癌的生物学行为.     

Correlation of caveolin-1 expression with microlymphatic vessel density in colorectal adenocarcinoma tissues and its correlation with prognosis

Objective: To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density(LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer. Methods: The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Muhivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time. Results: The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues(P0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues(P0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph nodemetastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. Conclusions: Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.     

Enhanced expression of endothelial nitric oxide synthase and caveolin-1 in human cirrhosis

BACKGROUND/AIMS: Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin-dependent nitric oxide synthases (NOS). Caveolin, the principal structural protein in caveolae, interacts with endothelial NOS (eNOS) leading to enzyme inhibition by a reversible process modulated by Ca++ -calmodulin. The aim of the present study was to examine the localizations of eNOS and caveolin-1 at protein level in normal human liver tissue, and how the expressions are altered in cirrhotic liver. METHODS: Fresh liver specimens were obtained from hepatic surgeries. Normal portions resected from cases of carcinoma metastasized to the liver were used as control specimens, and cirrhotic portions resected from cases of hepatocellular carcinoma with hepatitis C-related cirrhosis were used as cirrhotic specimens. Anti-eNOS and anticaveolin-1 antibodies were used for immunohistochemistry and Western blotting. Immunoelectron microscopy was conducted on ultra thin sections using immunoglobulin-gold combined with silver staining. RESULTS: Immunohistochemistry revealed that both eNOS and caveolin-1 were sparsely expressed on hepatic sinusoidal lining in normal liver specimens, and these findings were confirmed by Western blot. Both immunohistochemistry and Western blotting demonstrated over-expression of eNOS and caveolin-1 in cirrhotic liver specimens. Morphometric analysis of immunogold particle labeling for eNOS and caveolin-1 was performed on immunoelectron micrographs. In normal liver tissue, hepatic stellate cells and sinusoidal endothelial cells (SEC) expressed low levels of caveolin-1, and SEC expressed a very low level of eNOS. In cirrhotic liver, both caveolin-1 and eNOS expressions were significantly increased by approximately four-fold on SEC compared to normal liver. CONCLUSION: In cirrhotic human liver, marked increase of caveolin-1 in perisinusoidal cells may promote caveolin-eNOS binding and reduce the activity of eNOS despite an increased eNOS expression, leading to impaired NO production and increased hepatic microvascular tone.     

Caveolin-1在胃癌和癌前期变化中的表达及其意义

目的检测小凹蛋白-1(Caveolin-1)在胃腺癌(GAC)、癌前期变化及慢性浅表性胃炎(CSG)中的表达,探讨其生物学功能及其与GAC癌变和病理特征的关系。方法免疫组织化学S-P法检测59例GAC(其中:高分化9例,中分化25例,低分化25例;早期9例,进展期50例;无淋巴结转移30例,伴淋巴结转移29例)、30例CSG、80例癌前期变化包括30例慢性萎缩性胃炎(CAG)、30例肠上皮化生(IM)和20例异型增生(Dys),共169例组织中Caveolin-1的表达。结果Caveolin-1在CAG组、IM组、Dys组和GAC组中表达均高于CSG组,以GAC组表达最高(P0.05);IM组和Dys组表达无差异(P0.05)。Caveolin-1的表达程度与胃黏膜病变程度呈显著正相关(rs=0.792,P=0.000)。Caveolin-1在进展期及伴淋巴结转移的GAC组中高于早期及无淋巴结转移的GAC组(P0.05),但与肿瘤分化程度无关(P0.05)。结论Caveolin-1表达增高是GAC癌变和转移的重要分子事件,其影响可能在GAC发生的早期即已存在,并持续到GAC阶段,有望成为GAC淋巴结转移的预测指标。     

小窝蛋白1和血管内皮生长因子在结直肠癌组织中的表达及临床意义

目的:探讨小窝蛋白1(Cav-1)和血管内皮生长因子(VEGF)在结直肠癌组织中的表达,分析其与结直肠癌临床病理因素的关系及意义.方法:收集辽宁省肿瘤医院2007-01/2009-06肿瘤外科手术切除的83例结直肠癌标本及其配对正常结直肠组织（距癌灶边缘＞5 cm）.应用免疫组织化学SP法检测Cav-1和VEGF蛋白在...     

PD-L1 and HER2 expression in gastric adenocarcinoma and their prognostic significance

BackgroundThe upregulation of programmed death-ligand 1 (PD-L1) and epidermal growth factor receptor 2 (HER2) may play a role in gastric adenocarcinoma (GAC).AimTo study PD-L1 and HER-2 expression and prognosis in GAC.MethodsPD-L1 and HER2 expression was determined in tumor tissues of 75 patients with GAC. The correlations between PD-L1, HER2 expression, and clinicopathological factors were analyzed.ResultsThe positive expression rate for PD-L1 was 57.3% (43/75) and the HER2 over-expression rate was 17.3% (13/75). PD-L1 expression negatively correlated with the grade of GAC differentiation (r =-0.26, P<0.05). Approximately 85% of HER2-positive GACs were found to be PD-L1-positive and PD-L1 expression positively correlated with HER2 overexpression. The TNM stage and combined HER2 and PD-L1 expression were independent prognostic factors affecting the survival of patients with GAC. The median overall survival and recurrence-free survival of groups I (HER2 overexpression and PD-L1 positive), II (HER2 overexpression and PD-L1 negative), III (No HER2 overexpression and PD-L1 positive) and IV (No HER2 overexpression and PD-L1 negative) were (47 (17–77), 15 (0–44), 81 (62–101), and 78 (60–98) months, respectively.ConclusionPD-L1 expression is upregulated in more than half of patients with GAC. Anti-PD-L1 treatment combined with anti-HER2 therapy may benefit patients with locally advanced GAC with HER2 overexpression.