组织芯片技术在检测胃癌组织中TRAF4表达中的应用

目的探讨组织芯片技术诊断胃癌的价值。方法采用免疫组化法检测胃癌组织芯片（胃正常组织10份、增生组织45份、胃癌组织45份）中肿瘤坏死因子受体相关因子4（TRAF4）的表达。结果 TRAF4胞质阳性率在正常组织、增生组织和胃癌组织中逐渐增高,但差异无统计学意义。胞核阳性率逐渐降低,正常组织显著高于胃癌组织,P〈0.05;胃癌组织中高分化者显著高于低分化者（P〈0.05）,无淋巴转移者显著高于有淋巴转移者,P〈0.05。结论组织芯片可大规模、高效率检测胃癌组织样本,具有快速、方便、经济、准确等特点,可用于胃癌的早期诊断。     

HIF-1α及其调控基因PTEN在胃癌中表达的相互关系及临床病理意义

目的:探讨缺氧诱导因子-1α(HIF-1α)及其调控基因PTEN在胃癌及正常胃组织中表达的相互关系以及他们在胃癌的发生发展、浸润和转移中的作用.方法:应用免疫组化SP法检测54例胃癌组织中HIF-1α和PTEN的表达情况,探讨他们与胃癌临床病理因素的关系.结果:HIF-1α在胃癌中的表达率(74.07%)明显高于正常胃组织(0%)(P<0.01);HIF-1α的表达与胃癌TNM分期(P<0.05)、肿瘤浸润深度(P<0.01)和淋巴结转移显著相关(P<0.05).胃癌中PTEN低表达(51.9%),且在肿瘤浸润深(38.5%vs 86.7%,P<0.01)、有淋巴(28.0%vs 72.4%,P<0.01)和远隔转移(16.7%vs 61.9%,P<0.05)、临床分期高(28.6%vs 76.9%,P<0.01)、病理分化低(22.2%vs 70.6%,63.2%,P<0.01)的胃癌组织表达明显降低.胃癌组织中HIF-1α与PTEN的表达呈负相关(r=-0.41,P<0.05).结论:HIF-1α和PTEN在胃癌的发生发展中起重要作用,联合检测可作为判断胃癌恶性程度和预后的指标.     

胃癌组织TRAF3、TRAF6阳性表达及意义

目的探讨胃癌组织肿瘤坏死因子受体相关因子3(TRAF3)、肿瘤坏死因子受体相关因子6(TRAF6)阳性表达与肿瘤浸润、转移的关系。方法选择胃癌组织及配对癌旁正常组织标本各87份。制作组织芯片,采用免疫组化微阵列技术检测TRAF3、TRAF6表达,分析TRAF3、TRAF6阳性表达与胃癌浸润、转移的关系。结果胃癌组织TRAF3阳性表达率明显低于癌旁正常组织(P<0.01),TRAF6阳性表达高于癌旁正常组织(P<0.05)。TRAF3阳性表达与胃癌组织分化程度、TNM分期、淋巴结转移有关(P均<0.05),TRAF6阳性表达与胃癌组织分化程度、TNM分期有关(P均<0.05)。结论胃癌组织TRAF3阳性表达下调、TRAF6阳性表达上调,其表达变化可能参与胃癌的浸润及转移。     

P53和Ki67在胃癌中的表达及其临床意义

目的:探讨胃癌中P53和Ki67蛋白表达与临床病理参数的相关性及其临床意义.方法:收集在中国人民解放军南京军区福州总医院手术切除的胃癌组织标本1107例,采用EliVisionTM plus免疫组织化学染色方法检测其中临床资料完整的775例胃腺癌标本中Ki67和P53蛋白表达.结果:在775例胃腺癌组织标本中,P53和Ki67蛋白的阳性表达率分别为46.84%和78.97%,在非肿瘤性胃黏膜中均未见其阳性表达;P53和Ki67蛋白表达,在肠型胃癌中显著高于弥漫型胃癌(54.7%vs38.0%;86.0%vs70.0%,均P<0.05),高中分化胃癌显著高于低分化胃癌(54.7%vs35.4%;87.0%vs67.2%,均P<0.05);P53蛋白表达在胃食管连接部胃癌和无远处转移的胃癌中显著高于胃部胃癌和有远处转移的胃癌(53.7%vs41.9%;49.0%vs30.3%,均P<0.05);Ki67蛋白表达随着浸润深度的增加而增高(80.3%vs60.4%,P<0.05),有淋巴结转移的患者显著高于无淋巴结转移的患者(81.4%vs72.6%,P<0.05).结论:联合检测P53和Ki67蛋白表达有助于阐释胃...     

MMP-7与Fas蛋白在胃癌组织中的表达及意义

目的:探讨基质金属蛋白酶-7(MMP-7)蛋白和Fas蛋白在胃癌组织中的表达、相互关系及意义.方法:应用免疫组化方法检测了82例胃癌组织及30例周边正常胃黏膜中MMP-7和Fas的表达情况.结果:胃癌组织中MMP-7蛋白阳性率显著高于正常胃黏膜(73.2%vs10%,P<0.001);正常胃黏膜中Fas蛋白阳性率显著高于胃癌组织(39.1%vs93.3%,P<0.001).MMP-7阳性表达率与淋巴结转移、TNM分期显著相关(P<0.001),而与肿瘤细胞分化程度无显著性相关.Fas蛋白阳性表达率与肿瘤细胞分化程度显著相关(P<0.05),而与淋巴结转移、TNM分期无显著性相关.胃癌组织中MMP-7与Fas表达具有显著等级负相关(r=-0.597,P<0.001).结论:MMP-7与Fas表达胃癌的生物学行为密切相关,且两者之间的表达强度具有显著等级负相关.     

HIF-1α在中老年胃癌早期中的临床意义

目的探讨低氧诱导因子(HIF)-1α在胃癌组织及转移淋巴结中的表达情况及在中老年胃癌早期发生、发展、转移及预后中的作用及意义。方法对临床未进行化疗的60例胃癌患者切除的胃癌组织及转移淋巴结进行苏木素-伊红(HE)染色确定标本的组织分化程度,采用免疫组织化学方法检测HIF-1α在胃癌组织及转移淋巴结中的表达情况。结果 HIF-1α在胃癌组织中的阳性率为71.67%(43/60),转移淋巴结中的阳性率为86.7%(52/60),而正常胃组织仅有2列表达弱阳性,正常淋巴结中均未有阳性率表达,有显著差异(P<0.05),其中高分化阳性率为55%(11/20),中分化为65%(13/20),低分化为95.0%(19/20),差异有统计学意义(P<0.05)。结论 HIF-1α在胃癌中呈高表达,与胃癌新生血管形成、癌组织浸润、转移有密不可分的关系。     

Wnt信号通路的组件蛋白DKK-1、β-链接素及周期素D1蛋白表达与胃癌的相关性

目的探讨Wnt信号通路中的组件蛋白DKK-1、β-catenin及周期素(Cyclin)D1在胃癌的发生、发展及转移的相互关系。方法采用免疫组织化学方法标记DKK-1、β-catenin及Cyclin D1蛋白在80例胃癌组织标本,10例正常胃组织中的表达情况。结果 1DKK-1在胃癌组织中的表达明显低于胃正常组织(P0.05),高、中分化胃癌的表达高于低分化胃癌的表达(P0.05),伴有淋巴结转移的胃癌组织DKK-1较无转移病例阳性率低(P0.05)。2β-catenin在胃癌组织中的阳性表达率明显高于胃正常组织(P0.05),高、中分化胃癌的表达低于低分化胃癌的表达(P0.05),伴有淋巴结转移的胃癌组织β-catenin较无转移病例阳性率高(P0.05)。3Cyclin D1在胃癌组织中的表达明显高于胃正常组织(P0.05),高、中分化胃癌的表达低于低分化胃癌的表达(P0.05),伴有淋巴结转移的胃癌组织Cyclin D1较无转移病例阳性率较高(P0.05)。4在胃癌组织中DKK-1与Cyclin D1呈负相关关系(r=-0.453,P0.01),DKK-1与β-catenin呈负相关关系(r=-0.553,P0.01),Cyclin D1与β-catenin呈正相关关系(r=0.562,P0.05)。结论 Wnt信号通路中的组件蛋白DKK-1、β-catenin及Cyclin D1在胃癌的发生、发展及转移有一定的相互关系。     

胃癌组织中β-catenin及Tiam-1 mRNA表达的意义

目的:研究胃癌组织中β-catenin和Tiam-1的表达及二者与胃癌分化程度及转移的关系.方法:收集胃癌40例及慢性浅表性胃炎(CSG)组织30例,利用逆转录酶链式反应(RT- PCR)方法分别检测组织中β-catenin和Tiam-1 mRNA的表达情况.结果:在胃癌组织40例中24例有β-catenin mRNA表达(60.0%),β-catenin mRNA的表达与胃癌分化程度及淋巴结转移无关(P>0.05),在CSG 30例中16例有β-catenin mRNA表达(53.3%),2组比较,差异无统计学意义(χ~2= 0.3111,P>0.05).在胃癌组织40例中27例有Tiam-1 mRNA的表达(67.5%),在CSG 30例中8例有Tiam-1 mRNA的表达(26.7%),胃癌组织中Tiam-1的阳性率明显高于CSG组(χ~2= 11.4333,P<0.01),低分化组及淋巴结转移阳性组Tiam-1的阳性率高于高分化组及淋巴结转移阴性组(85.0%vs 50.0%,82.6%vs 47.1%,均P<0.05).结论:β-catenin mRNA表达与胃癌分化程度及转移无关,Tiam-1 mRNA表达与胃癌分化程度及淋巴结转移有关.     

p16基因高甲基化在胃癌发展中的作用

目的:通过检测胃癌、癌前病变和正常对照组中p16基因启动子区CpG岛甲基化水平及其表达,并结合临床病理资料,分析他们在胃癌发生、发展中的作用.方法:用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)检测41例胃癌组织、40例癌前病变组织和38例正常对照组织中p16基因启动子5′CpG岛甲基化;应用免疫组化检测基因的蛋白表达.结果:胃癌组织中p16基因甲基化阳性率为56.1%(23/41),癌前病变组织中为17.5%(7/40),而正常对照组织中为2.6%(1/38),前组与后两组之间的差异有显著性(P<0.05).胃癌组织中p16基因表达阳性率为51.2%,癌前病变组织中为90.0%,正常对照组织中为100.0%,前组与后两组之间的差异有显著性(P<0.05).低分化型胃癌组织中的p16基因甲基化阳性率明显高于高分化型(81.3%vs 40.0%,P<0.05).有淋巴结转移的胃癌组织中,p16基因甲基化阳性率与无转移组的差异有显著性(81.0%vs 30.0%,P<0.05).浸润深达浆膜层的胃癌组织中,甲基化阳性率与未达浆膜层组无统计学差异(60.0%vs 52.4%,P>0.05).胃癌组织中p16基因甲基化阳性组的蛋白表达阳性率显著低于甲基化阴性组(26.1%vs 83.3%,P<0.01).结论:胃癌组织中存在有p16基因启动子5′CpG岛高甲基化,并导致其基因表达率显著低于正常对照及癌前病变组织.p16基因的高甲基化与胃癌分化程度、淋巴结转移相关.p16基因甲基化的发生,从正常、癌前病变到胃癌有逐渐增加的趋势,提示其基因CpG岛高甲基化有可能作为诊断早期胃癌的一项较为敏感的指标.     

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.     

TFF2在胃癌、癌旁及正常胃黏膜组织中的表达及其与血管生成的关系

目的:探讨三叶因子2(TFF2)、血管内皮生长因子(VEGF)和微血管密度(MVD)在胃癌发生、发展、浸润和转移中的作用.方法:选取广西医科大学第一附属医院2008-01/2009-06接受胃大部切除术的胃癌标本50例,采用SP免疫组织化学方法检测30例正常胃黏膜组织、50例癌旁组织和50例胃癌组织中TFF2、VEGF...     

胃癌组织中CTGF蛋白表达及其临床意义

目的探讨结缔组织生长因子（CTGF）蛋自在胃癌发生、发展中的作用。方法采用免疫组化法检测10份正常胃黏膜组织、50份胃癌组织及其癌旁组织中CTGF蛋白表达情况。结果胃癌组织中CTGF阳性表达高于癌旁组织及正常胃黏膜组织,P〈0．05;癌组织CTGF阳性表达率明显高于正常黏膜组织（P〈0．01）,CTGF的高表达与胃癌分化程度、淋巴结转移密切相关（P均〈0．05）;与肿瘤浸润的深度无明显关系。结论CTGF蛋白可作为胃癌前病变及胃癌早期诊断和预后判断的指标。     

胃癌组织MMP-10和VEGF表达与血管生成的关系

目的:研究胃癌组织中基质金属蛋白酶- 10(MMP-10)、血管内皮生长因子(VEGF)和微血管密度(MVD)表达变化及其与肿瘤临床病理特征之间的关系.方法:以CD31作为MVD指标,应用免疫组化法检测60例胃癌组织和60例距病灶5 cm以上的正常组织中的MMP-10、VEGF和CD31的表达并对结果进行分析.结果:60例胃癌组织中的MMP-10、VEGF的表达阳性率分别为81.7%、76.7%,明显高于正常组织的表达阳性率11.7%、8.3%,两者差异有统计学意义(P<0.05).MMP-10、VEGF的表达与MVD、与肿瘤的分化程度、TNM分型、淋巴结的转移、浸润程度有关.结论:MMP-10、VEGF胃癌组织中高表达与胃癌侵袭转移、血管生成密切相关,可作为判断胃癌侵袭转移及预后的重要指标.     

Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue

AIM: To investigate whether NF-kB is activated in human gastric carcinoma tissues and, if so, to study whether there is any correlation between NF-kB activity and heparanase expression in gastric carcinoma. METHODS: NF-kB activation was assayed by immunohistochemical staining in formalin-fixed, paraffin-embedded specimens from 45 gastric carcinoma patients. Electrophoretic mobility shift assay (EMSA) method was used for nuclear protein from these fresh tissue specimens. Heparanase gene expression was quantified using quantitative RT-PCR. RESULTS: The nuclear translocation of RelA (marker of NF-kB activation) was significantly higher in tumor cells compared to adjacent and normal epithelial cells [(41.3±3.52)% vs (0.38±0.22) %, t=10.993, P= 0.000<0.05; (41.3±3.52)% vs(0±0.31)%, t=11.484, P= 0.000<0.05]. NF-kB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion, pathological stage, and depth of invasion (Z= 2.148, P= 0.032<0.05; t = 8.758, P= 0.033<0.05; t = 18.531, P = 0.006<0.05). NF-KB activation was significantly correlated with expression of heparanase gene (r= 0.194, P=0.046<0.05). CONCLUSION: NF-KB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. This suggests NF-kB as a major controller of the metastatic phenotype through its reciprocal regulation of some metastasis-related genes.     

胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

Expression and correlation of CD44v6, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 in Krukenberg tumor

AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: x2 = 4.516, P= 0.034; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 19.537, P= 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: x2 = 22.895, P= 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 (x2 = 10.398, P= 0.001), VEGF (x2 = 13.149, P= 0.001), MMP-2 (x2= 33.668, P= 0.001) and MMP-9 (x2 = 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.     

High expression of TRAF4 in hepatocelullar carcinoma as an independent negative survival and recurrence predictor

Objective: To identify potential tumor markers for the development and recurrence of hepatocelullar carcinoma(HCC), this research studied the relationship between the expression of the tumor necrosis factor receptor-associated factor 4(TRAF4) and tumor angiogenesis together with its survival time of HCC patients. Methods: The expressions of TRAF4,vascular endothelial growth factor and CD34 were performed upon 90 patients with curative liver resection between August 2006 and November 2009 by immunohistochemical method in locally advanced HCC and adjacent non-tumoral liver. The expression of TRAF4 was determined by the Spearman rank correlation. Their prognostic factors on disease free survival(DFS) and overall survival(OS) were guaranteed by Kaplan-Meier and Cox regression analyses. The detection of the levels of vascular endothelial growth factor and CD34 was fulfilled in 90 cases of HCC. Results: TRAF4 expression was both significantly higher in HCC than in surrounding non-tumor tissues(57.8% vs. 22.2 %; P0.001) and significantly correlated with tumor size and tumor staging. High TRAF4 was correlated with reduced DFS rate(P=0.001) and overall OS rate(P0.001) and were displayed in Kaplan-Meier survival analysis. Conclusions: TRAF4 is involved with multifarious clinicopathologic features.TRAF4 expression, as an independent adverse prognostic factor, DFS and OS in HCC, is associated with increased tumor angiogenesis. The combined detection of TRAF4 in locally advanced HCC is a trustworthy predictive factor for the tumor development and recurrence.     

Distribution of thymidine phosphorylase activity in gastric carcinoma and adjacent normal gastric tissue

BACKGROUND/AIMS: Thymidine phosphorylase was reported to be identical to the angiogenic factor, platelet-derived endothelial cell growth factor. In this study we investigated the distribution of thymidine phosphorylase activity in human gastric carcinoma or normal gastric tissue using the ELISA system. METHODOLOGY: A longitudinal slice in the center of the gastric carcinoma of resected specimens from 6 patients with gastric carcinoma was used, and thymidine phosphorylase activity was mapped in each case. RESULTS: In all cases, the thymidine phosphorylase activities were significantly higher in tumors than adjacent normal gastric tissues. The amount and distribution of thymidine phosphorylase activity were different between intestinal-type and diffuse-type carcinoma. The thymidine phosphorylase activities in the invasive front of tumor were significantly lower than those in the other part in intestinal-type carcinoma. CONCLUSIONS: The ELISA system used in this study proved useful for the determination of thymidine phosphorylase activities in tissue sections.