Correlation of P-glycoprotein expression with poor vascularization in human gallbladder carcinomas

AIM: To investigate the relationship between the expression of P-glycoprotein (P-gp) and the degree of vascularization in gallbladder carcinomas.METHODS: P-gp was stained with streptavidin-peroxidase complex immunohistochemical method in routine paraffinembedded sections of gallbladder carcinomas. Microvessel counts (MVC) were determined using factor-Ⅷ-related antigens.RESULTS: The average MVC in 32 cases of gallbladder carcinomas was (34±10)/HP. The value of MVC was closely correlated with Nevin staging and tumor differentiation (P＜0.01 and P＜0.05). The total expression rate of P-gp was 62.5 %. The P-gp expression rate in cases of Nevin staging S1-S3 (78.6 %) was higher than that of S4-S5 (50.0 %) with no statistical significance. The P-gp expression rate was not correlated with tumor differentiation or pathologic types. The value of MVC in P-gp (+) cases was markedly lower than that in P-gp (-) cases (P＜0.01). The positive rate of P-gp was significantly higher in cases of smaller MVC than those of bigger MVC (P＜0.05).CONCLUSION: MVC may be used as one of the important parameters to reflect the biological behaviors of gallbladder carcinomas. As a major cause of drug resistance, the overexpression of P-gp is closely correlated with the poor vascularization in gallbladder carcinomas.     

Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma

AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape. METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues, 18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma. RESULTS: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (X^2= 4.89, P<0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t‘= 4.19, P=<0.01) and chronic cholecystitis (t‘= 8.06, P=<0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma than that in poorly-differentiated carcinoma (t‘= 2.63, P=<0.05) and Nevin Ⅳ-Ⅴ carcinoma (t‘= 3.33, P<0.01). The confidence interval (CI) of infiltrating lymphooltes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma was very significantly lower than that in carcinoma (t‘ = 6.99, P<0.01), adenoma (t‘ = 3.66, P<0.01), poorly-differentiated carcinoma (t‘ = 5.31, P<0.01) and Nevin Ⅳ-Ⅴ carcinoma (t‘ = 3.76, P<0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P<0.05), and was not significantly lower in Nevin Ⅰ-Ⅲ carcinoma than in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P>0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.     

Association of cyclin D1, p16 and retinoblastoma protein expressions with prognosis and metastasis of gallbladder carcinoma

AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma. METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading. RESULTS: The expression rates of abnormal cyclin Dl in gallbladder carcinoma (68.3%)and gallbladder adenoma (57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G1, G2 and G3 and among Nevin stagings S1-S2, S3 and S4-S5 of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S1-S2 (80.0% and 90.0%) and S3 (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S4-S5(33.3% and 38.8%) (P<0.05), and those in pathologic grades G1(54.5% and 81.8%) and G2 (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G3 (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r= -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin Dl had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05). CONCLUSION: Cyclin Dl may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.     

Analysis of p53 and vascular endothelial growth factor expression in human gallbladder carcinoma for the determination of tumor vascularity

AIM:To examine the expression of p53 and vascularendothelial growth factor(VEGF)as well as microvesselcount(MVC)and to investigate the role of VEGF asan angiogenic marker and the possible role of p53 inthe regulation of angiogenesis in human gallbladdercarcinoma.METHODS:Surgically resected specimensof 49 gallbladder carcinomas were studied byimmunohistochemical staining for p53 protein,VEGF,andfactor Ⅷ-related antigen.VEGF expression and mutantp53 expression were then correlated with Nevin stage,differentiation grade,MVC,and lymph node metastasis.RESULTS:Positive p53 protein and VEGF expressionswere found in 61.2% and 63.3% of tumors,respectively.p53 and VEGF staining status was identical in 55.1%of tumors.The Nevin staging of p53-or VEGF-positivetumors was significantly later than that of negativetumors.The MVC in p53-or VEGF-positive tumorswas significantly higher than that in negative tumors,and MVC in both p53-and VEGF-negative tumors wassignificantly lower than that in the other subgroups.CONCLUSION:Our findings suggest that p53-VEGFpathway can regulate tumor angiogenesis in humangallbladder carcinoma.Combined analysis of p53 andVEGF expression might be useful for predicting thetumor vascularity of gallbladder cancer.     

血管内皮细胞生长因子的表达及微血管密度与胆囊癌浸润、转移及预后的相关研究

探讨血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)及微血管密度 (Microvesseldensity ,MVD)在胆囊癌发生发展中的作用及与胆囊癌浸润、转移及预后的关系。应用S -P免疫组化技术对 3 1例经手术切除的原发性胆囊癌及 10例经手术切除的慢性胆囊炎标本进行VEGF蛋白和微血管密度检测。 3 1例胆囊癌组织中癌旁VEGF表达及MVD值均明显高于癌中央及正常组织 ,三者差异具有显著性 (P <0 0 1) ;VEGF表达与MVD具有相关性 ,VEGF阳性者MVD值显著高于阴性者 (P <0 0 1) ;VEGF表达和MVD与胆囊癌分化程度、浸润转移、Nevin分期密切相关 (P <0 0 1) ;VEGF阳性者及高MVD者预后较阴性者差 ;Cox比例危险模型多因素分析表明 :VEGF对胆囊癌是一个独立的预后因子。VEGF的表达及MVD在胆囊癌的发生和浸润转移过程中发挥重要的作用 ,VEGF和MVD可作为反映胆囊癌生物学行为的指标     

COX-2、VEGF在子宫内膜癌中的表达及意义

目的 探讨环氧化酶-2（COX-2）和血管内皮生长因子（VEGF）在子宫内膜癌发生发展中的作用。方法 采用免疫组化SP法检测41例子宫内膜癌和15例正常子宫内膜组织中COX-2、VEGF的表达。结果 子宫内膜癌组织中COX-2、VEGF的阳性表达率明显高于正常子宫内膜组织（P均〈0．05,）;低分化和肌层浸润〉1／2者的子宫内膜癌组织中COX-2表达明显高于中、高分化和肌层浸润≤1／2（P〈0．05）者;COX-2表达阳性的子宫内膜癌,其VEGF阳性率明显高于COX-2表达阴性者（P〈0．05）。结论 COX-2在子宫内膜癌组织中呈高表达,并可上调VEGF的表达,二者可能与子宫内膜癌的发生发展有关。     

Relationship between inducible nitric oxide synthase expression and angiogenesis in primary gallbladder carcinoma tissue

AIM:To explore the relationship between angiogenesis and biological behaviors of primary gallbladder carcinoma (PGBC),the relationship between the expression of inducible nitric oxide synthase (iNOS) and biological behaviors of PGBC and its relationship with the expression of iNOS and angiogenesis of PGBC.METHODS: The expression of iNOS and micro-vessel density (MVD) were assessed by immunohistochemical method and image analysis system in 40 specimens of PGBC and in 8 specimens of normal gallbladder. The immunostaining results and related clinicopathologic materials were analyzed by statistical methods.RESULTS: MVD in PGBC was significantly higher than that in normal gallbladder tissue (46&#177;14 vs 14&#177;6, P&lt;0.05), and was not related with age, gender, tumor size and histological type. MVD of poorly and undifferentiated tumor tissues was higher than that of moderately-differentiated and well-differentiated tumor tissues (52&#177;9 vs43&#177;9 vs33&#177;6, P&lt;0.01).MVD of Nevin IV and V stages was higher than that of NevinI, Ⅱ and Ⅲ stages (52&#177;8 vs 37&#177;13, P&lt;0.01). MVD of cases with lymphatic or liver metastasis was significantly higher than that without liver metastasis (55&#177;6 vs 42&#177;10, P&lt;0.05) or lymphatic metastasis (53&#177;8 vs38&#177;8, P&lt;0.01). The positive level index (PLI) of iNOS in PGBC was 0.435&#177;0.134, and was not related with age, gender, tumor size, histological type,differentiation and clinical stage of PGBC. The PLI of iNOS in cases with lymphatic metastasis was higher than that without lymphatic metastasis (0.573&#177;0.078 vs 0.367&#177;0.064,P&lt;0.01). The PLI of iNOS in cases with liver metastasis was higher than that without liver metastasis (0.533&#177;0.067 vs0.424&#177;0.084, P&lt;0.05). There was a significant correlation between PLI of iNOS and MVD in PGBC (P&lt;0.05).CONCLUSION:Angiogenesis of PGBC is significantly related to the biological behaviors of PGBC. The expression of iNOS is related to the biological behaviors of PGBC. The detection of MVD and the expression of iNOS in PGBC can be used as parameters to determine the degree of malignancy and prognosis.     

PTTG和bFGF在原发性胆囊癌中表达及意义

探讨垂体肿瘤转化基因 (PituitaryTumorTransformingGene ,PTTG)和碱性成纤维细胞生长因子 (basicFi broblastGrowthFactor,bFGF)在原发性胆囊癌中的表达及相互关系 ,研究它们的表达与肿瘤临床病理指标及预后的联系。应用免疫组织化学 ,检测 4 1例原发性胆囊癌及 2 0例慢性结石性胆囊炎中PTTG和bFGF的表达水平。在原发性胆囊癌中PTTG和bFGF阳性表达率分别为 85 4 %、5 6 1% ,其阳性率及表达等级均明显高于慢性胆囊炎 (P <0 0 1)。PTTG和bFGF表达等级均与胆囊癌的Nevin分期和淋巴结转移密切相关 (P <0 0 5或P <0 0 1) ;PTTG表达与bFGF表达成等级正相关 (r =0 5 2 6 ,P <0 0 1)。PTTG或bFGF阳性患者的累计生存期明显低于阴性者 (P <0 0 5 )。PTTG或bFGF与胆囊癌生物学行为及预后有密切关系 ,二者的联合检测 ,有助于原发性胆囊癌恶性程度和预后的判断     

凋亡相关基因survivin、bcl-2及caspase-3在胆囊癌中的表达及意义

目的探讨凋亡相关基因survivin、bcl-2及caspase-3在胆囊癌中的表达及其在胆囊癌发生、发展的可能作用及相互关系。方法应用免疫组织化学SABC法,检测39例胆囊癌组织、15例胆囊腺瘤组织和12例慢性胆囊炎组织中survivin、bcl-2及caspase-3表达情况,分析其与胆囊癌临床病理的关系,并探讨survivin、bcl-2及caspase-3表达在胆囊癌中的相关性。结果survivin在胆囊癌中的阳性表达率为71.8%,而在胆囊腺瘤及慢性胆囊炎中均无表达;bcl-2在胆囊癌中的表达阳性率为71.8%,而在胆囊腺瘤及慢性胆囊炎中均无表达;bcl-2在胆囊癌中的表达阳性率为38.5%,在胆囊腺瘤中为93.3%,在慢性胆囊炎中为8.3%,胆囊腺瘤bcl-2表达明显高于胆囊癌(P<0.01),胆囊癌bcl-2表达明显高于慢性胆囊炎组织(P<0.05)。caspase-3在胆囊癌中的表达阳性率为43.6%,胆囊腺瘤及慢性胆囊炎中caspase-3表达率均为100%。survivin表达与患者的临床病理无关。bcl-2及caspase-3的表达与胆囊癌患者的性别、年龄、肿瘤的大小无关,而阳性率在组织分化程度、不同Nevin分期组间差异有显著性(P<0.05)。survivin与bcl-2及caspase-3表达没有相关性(P>0.05),bcl-2与caspase-3表达具有良好的相关性(P<0.05)。结论survivin和bcl-2在胆囊癌中有较高表达,而caspase-3在胆囊癌中的表达下降;bcl-2与caspase-3可反映胆囊癌的某些临床病理特点;survivin、bcl-2及caspase-3共同调节胆囊癌细胞凋亡,进而影响胆囊癌的发生、发展。     

Significance of cyclooxygenase—2 expression in human primary hepatocellular carcinoma

AIM：To clarife the significance of cyclooxygenase-2(COX-2)expression in human primary hepatcellular carcinoma(HCC)and adjacent nontumorous tissues.METHODS;TheCOX-2protein and mRNA were investigated in 27HCC tissues with adjacent nontumorous tissues,and 5histologically normal liver tissues,using immunohistochemistry and in situ hybridization.RESULTS:The well-differentiated HCC expressed COX-2protein(5.68&#177;1.19)more strongly than moderated HCC(3.43&#177;1.98)and poor differentiated HCC(3.33&#177;1.50)(P&lt;0.05 respectively),adjacent nontumorous tissues(4.93&#177;1.05)and normal live tissues(3.20&#177;1.92)(P&lt;0.01 respectively);More intensive staining of COX-2in adjacent nontumorous tissues was observed than that in normal liver tissues(P&lt;0.05).There was no significant difference among adjacent nontumorous tissues,moderately differentiated HCC and poorly differentiated HCC(P&gt;0.05).The expression of COX-2mRNA was observed in the cytoplasm of the cells of HCC and of gtthe hepatocytes in adjacent nontumorous tissues in which COX-2 protein was positive.CONCLUSION:The overexpression of COX-2 in well-differentiated HCsuggets that COX-2 may play a role in the early stages of hepatocarcinogensis.     

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages Ⅲ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages Ⅰ-Ⅱ and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2-positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.     

肺癌桩蛋白与血管内皮生长因子的表达及其临床意义

目的　探讨桩蛋白 (PAX)和血管内皮生长因子 (VEGF)在人肺部组织中的表达及其与组织学类型、组织学分级、淋巴结转移及预后的关系。方法　应用免疫组化的方法检测 79例肺癌组织中PAX和VEGF表达的情况。结果　 1、79例肺癌组织PAX和VEGF的阳性率为 3 4 1%和 64 6% ;2、PAX的阳性率与肺癌的淋巴结呈正相关 (P <0 0 5 ) ,与 2年生存率无关 (P >0 0 5 ) ;3、VEGF的阳性率与淋巴结转移呈正相关 (P <0 0 1) ,与 2年生存率呈负相关 (P <0 0 1)。结论　PAX和VEGF在肺癌的转移中有重要作用 ;VEGF还影响着肺癌的预后     

结肠癌及癌前病变组织中COX-2及VEGF的表达

目的: 探讨结肠癌及癌前病变中COX-2和血管内皮生长因子(VEGF)的表达意义.方法:应用免疫组织化学ABC法检测COX-2及VEGF在40例癌旁正常结肠黏膜和结肠癌、27例结肠腺瘤组织中COX-2和VEGF的表达.结果: 结肠腺瘤和结肠癌组COX-2阳性表达率明显高于癌旁正常结肠黏膜组(63.0%, 77.5% vs 0.0%, 0.0%;P<0.05). 结肠腺瘤和结肠癌组VEGF阳性表达率明显高于癌旁正常结肠黏膜组(70.4%, 80.0% vs 25.0%, 25.0%;P<0.05), 且二者表达有相关性(r = 0.411, P<0.01). 结论:COX-2和VEGF在结肠腺瘤及结肠癌中表达异常增高.     

Survivin、COX-2和VEGF在胃癌中的表达及其与预后的意义

目的研究生存素(Survivin)、环氧合酶-2(COX-2)和血管内皮生长因子(VEGF)在胃癌组织中的表达,探讨它们表达的关系及其与胃癌预后的关系。方法选取淮南东方医院集团总医院1992~2002年10年间行根治性手术治疗,临床、病理和随访资料齐全的胃癌患者65例,应用免疫组化S-P技术,检测Survivin、COX-2和VEGF在胃癌组织中表达。结果早期胃癌的5年生存率为95.2%(20/21),中期胃癌的5年生存率为63.6%(7/11)。中期胃癌组Survivin阳性表达高于早期胃癌组(73.6%vs 66.7%,P<0.05),其VEGF阳性表达和微血管密度(MVD)平均值高于早期胃癌组(P<0.05)。Survivin和COX-2在慢性萎缩性胃炎中的表达明显低于不典型增生者(P<0.05),在癌组织中的表达明显高于非癌组织(P<0.05)。胃癌组中的VEGF阳性表达率和MVD平均值均明显高于非癌组,且与胃癌浸润深度有关(P<0.05)。胃癌中Survivin、VEGF阳性表达的MVD值显著高于Survivin、VEGF阴性表达者(P<0.05);Survivin、COX-2、VEGF及MVD值与胃癌淋巴结转移、血管浸润均密切相关(P<0.05);Survivin、COX-2阳性表达及VEGF阳性表达者5年生存率明显低于阴性或低表达者(P<0.05)。多因素分析显示,淋巴结转移、浸润深度、Survivin表达、VEGF表达均为胃癌独立的预后因素。结论Survivin、COX-2、VEGF与胃癌的生长和浸润转移关系密切,可以作为反映胃癌生物学行为和判断预后的有效指标。     

Significance of vascular endothelial growth factor messenger RNA expression in gastric cancer

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老年胃癌患者区域转移淋巴结中COX-2与多药耐药因子相关性分析

目的探讨老年患者胃癌原发灶、区域淋巴结转移灶中环氧合酶-2(COX-2)与多药耐药因子P-糖蛋白(P-gp)、谷胱甘肽S转移酶-π(GST-π)及DNA拓扑异构酶Ⅱα(TopoⅡα)表达的关系及意义。方法免疫组化染色法检测33例伴区域淋巴结阳性转移的老年胃癌患者(≥60岁)标本中COX-2、P-gp、GST-π、TopoⅡα的表达情况,同法检测32例对照组(<60岁)胃癌原发灶、转移灶中4种蛋白的表达,比较其在两组患者之间、淋巴结转移灶与原发灶之间的强度表达差异,并进行相关分析。结果老年患者P-gp在转移灶表达高于原发灶(P<0.05),TopoⅡα则在转移灶中表达降低(P<0.05);TopoⅡα表达在原发灶、转移灶间存在正相关关系(r=0.499 3,P<0.01)。老年患者原发灶组织中COX-2与TopoⅡα之间存在负相关表达(r=-0.588 9,P<0.01),P-gp与TopoⅡα之间存在正相关表达(r=0.382 0,P<0.05);转移灶各因子表达间未发现相关关系(均P>0.05)。原发灶老年组COX-2、P-gp和GST-π表达明显高于对照组(均P<0.05);转移灶老年组COX-2、P-gp的表达高于对照组(均P<0.05)。结论老年胃癌患者与对照组比较,COX-2及部分多药耐药因子存在异质性表达,老年患者多药耐药性与其他年龄患者不同,对老年患者进行多药耐药性逆转的胃癌生物治疗应根据COX-2、多药耐药因子的表达特点进行。     

Relationship between the expression of iNOS,VEGF,tumor angiogenesis and gastric cancer

AIM：To in vestigate the relationship between the expression of inducible nitric oxide synthase(iNOS),vascular endothelial growth factor(VEGF),the microvascular density(MVD)and the pathological features and clinical staging of gastric cancer.METHODS:Immunohistochemical staining was used for detecting the expression of iNOS and VEGFin46resected specimens of gastric carcinoma;the monoclonal antibody against CD34 was used for displaying vascular endothelial cells,and MVD was detected by counting of CD34-positive vascular endothelial cells.RESULTS:Of 46resected specimens of gastric carcinoma,the rates of expressions of iNOS and VEGF were 58.70%and76.09%,respectively,and MVDaveraged55.59&#177;19.39,Judged by the standard TNM criteria,the rate of expression of iNOS in stageⅣ（84.46%)was higher than those in stageⅠ,Ⅱ,Ⅲ（Fish exact probabilities test,P=0.019,0.023and 0.033,respectively);the rates of expression of VEGFin stage Ⅲ,Ⅳ（76.0%,92.31%,respectively)were higher than those in stageⅠ,Ⅱ（Fis exact probabilities test,P=0.031,0.017,0.022and0.019).MVDs in stageⅢ,Ⅳ（64.72&#177;14.96,67.09&#177;18.29,respectively)were higher than those in stageⅠ,Ⅱ(t\2.378,4.015,2.503and2.450,P&lt;0.05,P&lt;0.001,P&lt;0.001,P&lt;0.05,respectively),In37gastric carcinoma specimens with lymph node metastasis,MVD(68.69&#177;18.07)and the rates of expression of iNOS and VEGF(70.27%,83.78%,respectively)were higher than those in the specimens with absence of metastasis(t=2.205,X^2=6.3587,X^2=6.2584,P&lt;0.01,P&lt;0.05,P&lt;0.05,respectively),MVD and the expressions of iNOS and EGF were not correlated to the location,size or grade of tumor,nor with the depth of invasion of tumor;MVDs in the positive iNOS and VEGF specimens(59.88&#177;18.02,58.39&#177;17.73,repectively)were higher than those in the negative iNOS and VEGF specimens(X^2=6.3587and 6.1574,P&lt;0.05,P&lt;0.05,respectively);thus the expressions of iNOS and VEGF was correlated to MVD,but the expression of iNOS was not correlated to that of VEGF,In addition.of the 46 surviving patients,the 5-year survival rate of patients with positive iNOS or VEGF tumors was significantly less than that of patients with negative iNOS-or VEGF tumors(X^2=4.3842and 5.4073,P&lt;0.05,P&lt;0.05.respectively).CONCLUSION:The expressions of iNOS and VEGF are colosely related to tumor angiogenesis,and are involved in the advancement and the lymph node metastasis;thusMVD and the expressions of iNOS and EGF may serve indexes for evaluating staging of gastric carcinoma and forecasting its risk of metastasis,which will help establish a comprehensive therapeutical measure of post-operative patients and provide a new approach to tumor therapy.     

Expression of COX-2 proteins in gastric mucosal lesions

AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions and to assess the relationship between COX-2 expression and type, pathologic stage, differentiation, or lymph node metastasis in gastric cancer and the relationship between COX-2 expression and H pylori infection in gastric mucosal lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical resection. Samples were taken from tumor site and paracancerous tissues, and ABC immunohistochemical staining was used to detect the expression of COX-2 proteins. H pylori was determined by rapid urea test combined with pathological stating/14C urea breath test. RESULTS: The positive rate and staining intensity of mutant COX-2 gene expression in gastric cancer were significantly higher than those in paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant correlation between COX-2 and pathologic stage or lymph node metastasis type of gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was found between COX-2 expression and type or grade of differentiation (P>0.05). COX-2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%, 60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large proportion of gastric cancer tissues compared with matched non-cancerous tissues and was significantly associated with advanced tumor stage and lymph node metastasis. Overexpression of COX-2 plays an important role in tumor progression of gastric cancer. COX-2 may also play a role in the early development/promotion of gastric carcinoma and is associated with H pylori infection.     

Correlation between expression of cyclooxygenase-2 and angiogenesis in human gastric adenocarcinoma

AIM: To evaluate the expression of cyclooxygenase (COX2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma.METHODS: Immunohistochemical stain was used for detecting the expression of COX-2 in 45 resected specimens of gastric adenocarcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of CD34-positive vascular endothelial cells. Paracancerous tissues were examined as control.RESULTS: Immunohistological staining with COX-2-specific polyclonal antibody showed cytoplasmic staining in the cancer cells, some atypical hyperplasia and intestinal metaplasia,as well as angiogenic vasculature present within the tumors and prexisting vasculature adjacent to cancer lesions. The rate of expression of COX-2 and MVD index in gastric cancers were significantly increased, compared with those in the paracancerous tissues (77.78 vs 33.33 %, 58.13±19.99 vs 24.02±10.28, P＜0.01, P＜0.05, respectively). In 36 gastric carcinoma specimens with lymph node metastasis, the rate of COX-2 expression and MVD were higher than those in the specimens without metostasis (86.11 vs 44.44 %,58.60±18.24 vs 43.54±15.05, P＜0.05, P＜0.05, respectively).The rate of COX-2 expression and MVD in the specimens with invasive serosa were significantly higher than those in the specimens without invasion to serosa (87.88 vs 50.0 %,57.01±18.79 vs42.35±14.65, P＜0.05, P＜0.05). Moreover,MVD in COX-2-positive specimens was higher than that in COX-2-negative specimens (61.29±14.31 vs 45.38±12.42,P＜0.05). COX-2 expression was positively correlated with MVD (r=0.63, P＜0.05).CONCLUSION: COX-2 expression might correlate with the occurance and advancement of gastric carcinoma and is involved in tumor angiogenesis in gastric carcinoma. It is likely that COX-2 by inducing angiogenesis can be one of mechanisms which promotes invasion and metastasis of gastric carcinoma. It may become a new therapeutic target for anti-angiogenesis.     

VEGF和CD44v6过表达与乳腺癌浸润转移的关系

目的检测血管内皮生长因子(VEGF)和转移相关黏附分子44v6(CD44v6)在乳腺癌中的表达情况,探讨两者与淋巴结转移的关系。方法采用免疫组化SP法检测92例乳腺浸润性癌中VEGF、CD44v6的表达情况。结果 VEGF在正常乳腺组织和乳腺癌中的阳性表达率分别为6.7%(3/45)和90.2%(83/92),且VEGF在淋巴结转移组中的阳性表达率(53/55)明显高于无淋巴结转移组(P<0.05)。CD44v6在正常乳腺组织及乳腺癌中的阳性表达率分别为8.9%(4/45)和85.9%(79/92),而且CD44v6在淋巴结转移组中的阳性表达率(51/55)明显高于无淋巴结转移组(P<0.05)。VEGF和CD44v6表达呈正相关关系(r=0.497,P<0.05)。结论 VEGF、CD44v6在乳腺癌组织中高表达,且均与淋巴结转移有关(P<0.05),两者可能在乳腺癌的远处转移中起协同作用。