乳腺癌组织中LVD、VEGF-C和MMP-9表达及其相关性

目的 检测乳腺浸润性导管癌(invasive ductal carcinoma,IDC)组织中的淋巴管密度(lymphatic vessel density,LVD)、VEGF-C及MMP-9的表达,探讨其临床意义.方法 收集80例乳腺IDC和20例乳腺增生性病变,应用免疫组化PV-6000两步法检测淋巴管内皮透明质酸受体1(LYVE-1)、VEGF-C和MMP-9的表达.结果 乳腺癌组织中LYVE-1标记的LVD、VEGF-C和MMP-9的表达明显高于乳腺增生性病变,差异均有统计学意义(P<0.01).LVD、VEGF-C与临床病理参数之间均无差异(P>0.05).MMP-9的表达水平在肿瘤直径>2 cm组和淋巴结转移阳性组明显升高(P<0.05和P<0.01);而在组织学分级之间表达的差异无统计学意义(P>0.05).LVD与VEGF-C的表达呈正相关关系(r=0.398,P<0.01);LVD和MMP-9之间无相关关系(P>0.05).结论 IDC中淋巴管生成增多,VEGF-C是乳腺癌中淋巴管生成的重要刺激因子,促进乳腺癌中淋巴管的生成;但乳腺癌淋巴管密度与淋巴道转移无关.MMP-9参与肿瘤的侵袭和转移的过程,促进乳腺癌淋巴道转移.     

Expression of caspase-3 and caspase-9 and their significance in breast cancer

目的 探讨caspase-3和caspase-9在乳腺癌发生、发展中的作用.方法 采用免疫组化SP法和原位杂交(ISH)技术检测80例乳腺浸润性导管癌(invasive duct carcinoma,IDC)、23例导管内癌(ductal carcinoma in situ,DCIS)、37例增生症和9例癌旁组织中caspase-3、caspase-9 mRNA和蛋白的表达.结果 caspase-3 mRNA在各组中的表达差异无统计学意义(P>0.05).caspase-3蛋白在IDC、DCIS、增生症中的表达均高于癌旁组织(P<0.05),在IDC、DCIS中的表达均高于增生症组(P<0.05).caspase-9 mRNA和蛋白在IDC、DCIS、增生症中的表达均低于癌旁组织(P<0.05),IDC、DCIS中的表达均低于增生症组(P<0.05).caspase-3、caspase-9蛋白在IDC与DCIS中的表达差异均无统计学意义(P>0.05).caspase-3蛋白与mRNA在DCIS和增生症中的表达呈正相关(r=0.429,r=0.563,P<0.05).caspase-9 mRNA与蛋白在各组中的表达均存在相关性(r=0.94,r=0.414,r=0.391,r=0.827,P<0.05).caspase-3、caspase-9 mRNA和蛋白的表达与肿瘤大小等临床病理参数无相关性(P>0.05).结论 caspase-3和caspase-9均参与乳腺导管癌的发生、发展.caspase-9蛋白表达降低,而caspase-3表达增高在乳腺癌的发生、发展过程中较常见;caspase-9表达降低可能与乳腺组织恶性转化有关.     

乳腺良、恶性病变组织中MMP-26蛋白的表达及其与ER的关系

目的检测基质金属蛋白酶-26(MMP-26)蛋白在人乳腺良、恶性病变组织中的表达,及其与部分临床指标的关系,分析MMP-26在肿瘤进展中的作用及临床意义,并探讨雌激素及其受体(ER)对MMP-26蛋白表达调节作用。方法应用免疫组化SP法,检测MMP-26蛋白在正常乳腺组织、乳腺增生症、原位癌和乳腺浸润性导管癌(IDC)中的表达,以及ER在IDC中的表达并进行评分,结果用INSTAT统计软件分析。结果6例正常乳腺组织和8例乳腺增生症中,分别有1例MMP-26呈弱阳性表达,阳性率分别为16.7%和12.5%。4例原位癌中MMP-26全部阳性表达。在67例IDC中,有41例MMP-26阳性表达,阳性率为61.2%。MMP-26的表达与发病年龄、肿瘤大小、病理学分级无关,而与淋巴结转移密切相关(P<0.05)。MMP-26蛋白在IDC的阳性表达与ER在癌组织中的表达呈明显的负相关(P<0.01)。结论MMP-26在肿瘤浸润和转移中发挥重要作用;MMP-26在IDC中的表达可能受雌激素及其受体的调节。     

乳腺癌VEGF、MMP-9及COX-2蛋白表达与淋巴道转移和血管生成的相关性

目的 通过检测血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)、环氧化酶-2(COX-2)在乳腺癌细胞中的表达情况来探讨它们与乳腺癌淋巴结转移和微血管密度(MVD)的关系.方法 采用免疫组化SP法检测74例乳腺浸润癌(有淋巴结转移者39例,无淋巴结转移者35例)中VEGF、MMP-9、COX-2和CD34的表达,并用多因素Cox比例风险模型分析患者的预后.结果 VEGF、MMP-9、COX-2的表达与MVD值在淋巴结转移组与无转移组之间的差异均具有显著性(P＜0.05),与乳腺癌淋巴结转移呈正相关;VEGF、MMP-9、COX-2蛋白表达与MVD值呈正相关(P＜0.05);COX-2的表达随着乳腺癌病理分级的增高而增强;MVD值高者生存时间短.结论 乳腺癌VEGF、MMP-9、COX-2蛋白表达与其淋巴道转移和MVD有关,检测这几种蛋白表达将有助于判断乳腺癌的转移潜能、血管生成能力及预后.     

维吾尔族女性乳腺增生性病变与癌变组织中Notch1基因甲基化的差异比较

目的比较维吾尔族女性乳腺导管增生性病变和导管癌变组织中Notch1基因甲基化的差异情况。方法应用MALDITOF MS定位和定量检测Notch1基因在维吾尔族乳腺普通型导管增生(usual ductal hyperplasia,UDH)、非典型性导管增生(atypical ductal hyperplasia,ADH)、导管原位癌(ductal carcinoma in situ,DCIS)、浸润性导管癌(invasive ductal carcinoma,IDC)中甲基化率的变化,分析其与临床病理特征的关系,采用免疫组化法检测Notch1蛋白表达并分析其与甲基化的关系。结果Notch1基因在UDH、ADH、DCIS、IDC的甲基化率逐渐降低(P0.05),13个Cp G位点中9个位点甲基化率明显下降(P0.05),其低甲基化率伴随着低分化、淋巴结转移和TNM高分期(P0.05),Notch1基因低甲基化率与Notch1蛋白表达呈负相关(P0.05)。结论 Notch1蛋白表达和甲基化率在乳腺导管的不同增生性病变及乳腺癌变组织中存在一定的差异,其生物学意义有待进一步研究。     

乳腺癌组织中Caveolin-1、MMP-2的表达及意义

目的 探讨Caveolin-1及MMP-2蛋白在乳腺癌及正常乳腺组织中的表达及两者的相关性.方法 采用EnVision法免疫组化检测86例乳腺癌及20例正常乳腺组织中Caveolin-1及MMP-2蛋白的表达.结果 乳腺癌中Caveolin-1的阳性率(52.3%)低于正常乳腺组织(95.0%)(P<0.05),而MMP-2的阳性率高于正常乳腺组织(P<0.05).Caveolin-1在乳腺癌的表达与淋巴结转移、临床分期相关(P<0.05),而与患者年龄、组织学分级及肿瘤大小无关(P>0.05).MMP-2在乳腺癌的表达与淋巴结转移、组织学分级及临床分期相关(P<0.05),而与患者年龄及肿瘤大小无关(P>0.05).在乳腺癌中Caveolin-1和MMP-2的表达呈负相关(r=-0.472,P<0.05).结论 Caveolin-1低表达与MMP-2过表达可能是乳腺组织恶性转变以及乳腺癌发生浸润转移的重要生物学标志,联合检测Caveolin-1和MMP-2对预测乳腺癌的浸润转移有重要意义.     

COX-2、VEGF在乳腺癌组织中的表达及临床意义

目的探讨血管内皮生长因子(VEGF)和环氧化酶-2(COX-2)在乳腺癌组织中的表达及其与临床病理特征之间的关系。方法应用免疫组化S-P法检测不同乳腺组织中VEGF和COX-2的表达情况。结果VEGF、COX-2在乳腺导管癌组织中的表达明显上调,与其在正常乳腺组织、纤维腺瘤组织中的表达相比差异显著(P<0.01)。VEGF、COX-2在乳腺浸润性导管癌中的阳性表达率高于其在乳腺导管癌中的阳性表达率。两组中COX-2的表达有显著性差异(77.1%vs40%,P<0.05),VEGF的表达无显著性差异(80.0%vs70%,P>0.05)。VEGF在乳腺浸润性导管癌的阳性表达与其临床分期、淋巴结转移密切相关(P<0.05,P<0.01),与肿瘤大小无关(P>0.05)。COX-2在乳腺浸润性导管癌中的阳性表达与其临床分期、淋巴结转移及肿瘤大小均无关(P>0.05)。VEGF、COX-2在乳腺导管癌中的表达呈正相关(r=0.98,P<0.05)。结论VEGF、COX-2的高表达在乳腺癌的发生发展过程中起重要的作用,可作为重要的生物学标志。     

乳腺浸润性导管癌中Livin和MMP-7的表达及临床意义

目的检测凋亡抑制蛋白家族新成员Livin和基质金属蛋白酶-7(matrix metallo proteinase 7,MMP-7)在乳腺浸润性导管癌组织中的表达,探讨两者表达的相关性及其临床意义。方法采用免疫组化SP法检测Livin和MMP-7在乳腺浸润性导管癌和癌旁乳腺组织中的表达,并分析两者表达的相关性及其与乳腺浸润性导管癌患者临床病理特征的关系。进一步应用Western blot法检测乳腺浸润性导管癌及其相应的癌旁乳腺组织中Livin和MMP-7蛋白的表达水平。结果 Livin和MMP-7在乳腺浸润性导管癌和癌旁乳腺组织中的阳性率分别为65%vs 10%和73.3%vs 25%,且两者在乳腺浸润性导管癌组织中的阳性率均高于癌旁乳腺组织(P0.05)。统计学分析显示,Livin表达与乳腺浸润性导管癌患者的淋巴结转移和TNM分期具有正相关性(P0.05),MMP-7表达与乳腺浸润性导管癌的淋巴结转移、组织学分级均具有正相关性(P0.05)。Livin与MMP-7表达具有正相关性(r=0.322,P=0.007)。Western blot结果也表明,Livin与MMP-7蛋白在乳腺浸润性导管癌组织中的表达水平均高于癌旁乳腺组织。结论 Livin和MMP-7表达与乳腺浸润性导管癌的转移有关,两者可能具有协同作用促进乳腺浸润性导管癌的发展演进。     

HIF-2α、VEGF、COX-2、MMP-9表达及其与肾细胞癌血管生成的关系分析

目的 探讨HIF-2α(缺氧诱导因子-20α)、VEGF(血管内皮生长因子)、COX-2(环氧化酶-2)、MMP-9(金属基质酶-9)表达及其与肾细胞癌血管生成的关系.方法 应用免疫组化方法,检测79例肾细胞癌手术切除标本的HIF-2α、VEGF、COX-2、MMP-9表达情况,并与MVD(微血管密度)表达进行关联性分析.结果 肾癌组织MMP-9、VEGF的表达均显著高于正常肾组织(P＜0.05);不同临床分期肾癌组织中的MMP-9、VEGF表达有明显差异(P＜0.05).MVD与VEGF、MMP-9蛋白表达呈显著正相关(r=0.381、0.375,P＜0.05);MVD与COX-2表达有关,COX-Z表达0级和4级MVD值最低,与1、2、3级之间比较差异有统计学意义(P＜0.05),0级与4级之间比较差异无统计学意义(P＞0.05),1、2、3级之间差别无统计学意义(P＞0.05).肾细胞癌中HIF-2α阳性组的MVD值高于HIF-2α阴性组中MVD值,差异有统计学意义(t=4.374,P＜0.05);Spearman等级相关分析发现,HIF-2α的表达与MVD间存在正相关关系(r=0.545,P＜0.01).结论 HIF-2α、VEGF、COX-2、MMP-9表达及其与肾细胞癌血管生成之间有明显相关性,在临床上可以根据相关基因表达情况而采取相应的干预措施.     

乳腺癌中caspase-3和caspase-9的表达及其意义

目的探讨caspase-3和caspase-9在乳腺癌发生、发展中的作用。方法采用免疫组化SP法和原位杂交(ISH)技术检测80例乳腺浸润性导管癌(invasive duct carcinoma,IDC)、23例导管内癌(ductal carcinoma in situ,DCIS)、37例增生症和9例癌旁组织中caspase-3、caspase-9 mRNA和蛋白的表达。结果 caspase-3 mRNA在各组中的表达差异无统计学意义(P>0.05)。caspase-3蛋白在IDC、DCIS、增生症中的表达均高于癌旁组织(P<0.05),在IDC、DCIS中的表达均高于增生症组(P<0.05)。caspase-9 mRNA和蛋白在IDC、DCIS、增生症中的表达均低于癌旁组织(P<0.05),IDC、DCIS中的表达均低于增生症组(P<0.05)。caspase-3、caspase-9蛋白在IDC与DCIS中的表达差异均无统计学意义(P>0.05)。caspase-3蛋白与mRNA在DCIS和增生症中的表达呈正相关(r=0.429,r=0.563,P<0.05)。caspase-9 mRNA与蛋白在各组中的表达均存在相关性(r=0.94,r=0.414,r=0.391,r=0.827,P<0.05)。caspase-3、caspase-9 mRNA和蛋白的表达与肿瘤大小等临床病理参数无相关性(P>0.05)。结论 caspase-3和caspase-9均参与乳腺导管癌的发生、发展。caspase-9蛋白表达降低,而caspase-3表达增高在乳腺癌的发生、发展过程中较常见;caspase-9表达降低可能与乳腺组织恶性转化有关。     

Association between focal adhesion kinase and matrix metalloproteinase-9 expression in prostate adenocarcinoma and their influence on the progression of prostatic adenocarcinoma

Focal adhesion kinase (FAK), a member of the non-receptor cytoplasmic tyrosine kinase family, is associated with the development and progression of cancer. Matrix metalloproteinase-9 (MMP-9) is directly involved in the degradation of the extracellular matrix, and basement membrane components promote cancer cell migration and invasion. There is a functional interaction among FAK, MMP-9 and vascular endothelial growth factor (VEGF), which leads to enhanced cancer angiogenesis, cancer cell invasion and progression of malignancy. FAK, MMP-9, VEGF and CD34-positive microvessel density (MVD) were examined in 100 patients with prostate adenocarcinoma using immunohistochemistry. The relationship among these proteins and their impact on angiogenesis and clinicopathological parameters were also evaluated. The FAK expression was found to be positively correlated with the Gleason score, WHO grade group, tumour stage, extracapsular extension and perineural invasion. The MMP-9 expression was positively correlated with the WHO grade group, tumour stage, extracapsular extension, positive surgical margin and lymphovascular and perineural invasion. The FAK expression was also positively correlated with MMP-9 expression and MVD. However, no correlation between FAK and VEGF expression was identified. The MMP-9 expression was positively correlated with FAK expression and MVD. Strong MMP-9 expression was associated with shorter disease-free survival. These results suggest that strong MMP-9 and FAK expressions play an essential role in the progression of prostate adenocarcinoma. Further investigations should be conducted to determine the importance of these proteins as therapeutic targets for patients with prostate adenocarcinomas.     

Immunohistochemical expression of angiogenic cytokines in childhood Hodgkin lymphoma

This immunohistochemical study was carried out to evaluate the role of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), their inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1), and microvessel density (MVD) in the clinicopathologic behavior of childhood Hodgkin's lymphoma (HL). Paraffin-embedded histologic sections from 15 children with HL were immunohistochemically stained with MMP-2, MMP-9, TIMP-1, VEGF, and CD31 antibodies to investigate the correlation between the expression of these markers and the clinicopathologic characteristics of HL. Expression of MMP-2 and VEGF in Hodgkin and Reed-Sternberg cells (HRS) was more frequent in nodular sclerosis than in other subtypes (p=0.07 and 0.08, respectively). None of the study parameters in HRS cell were associated with age, sex, disease stage, extranodal disease, and the occurrence of bulky tumor. There was a trend toward advanced stage in negative TIMP-1 staining in HRS cells (p=0.06). In reactive lymphocytes, MMP-2 expression was correlated with MVD (r=0.68, p=0.005), and MMP-9 expression was correlated with B symptoms (p=0.003). Also, low TIMP-1 expression in reactive lymphocytes was frequently found in patients with advanced stage (p=0.048). There was a positive correlation with the ratio of MMP-2 expression in reactive lymphocytes and MVD (r=0.68, p=0.005). Expression of MMP-9 in reactive lymphocytes was correlated with MVD without statistical significance (r=0.487, p=0.06). Our results suggest that, as in many solid tumors, angiogenesis and angiogenic factors may play an important role in childhood HL. Larger series of patients are needed to determine the prognostic value of angiogenesis in childhood HL.     

非小细胞肺癌组织中MMP-9、TIMP-1表达及意义

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制剂-1(TIMP-1)的表达及其生物学行为的关系.方法 应用免疫组织化学SP法检测76例NSCLC和癌旁正常组织中MMP-9、TIMP-1的表达,并分析其表达与肺癌组织类型、肿瘤大小、TNM分期、分化程度、淋巴结转移的相关性.结果 MMP-9、TIMP-1在肺癌组织中的阳性表达率明显高于癌旁正常组织(P<0.05).NSCLC中MMP-9、TIMP-1表达与肿瘤的分化程度、临床分期、淋巴结转移有相关性(P<0.05),与肿瘤病理分型无关(P>0.05).结论 检测NSCLC中组织的MMP-9、TIMP-1的表达对判断肿瘤的恶性程度和预后评估有一定的意义.     

脑星形细胞瘤MMP-9、Flt-1表达与微血管密度的关系及其意义

目的探讨不同组织学类型的脑星形细胞瘤MMP-9、Flt-1表达与微血管密度（MVD）和恶性程度的关系。方法采用免疫组化方法检测50例星形细胞瘤中MMP-9、Fit-1和CD34的表达，并通过CD34免疫组化结果测定肿瘤组织中MVD。结果MMP-9、Flt-1在各型脑星形细胞瘤中均有不同程度的表达；不同组织学类型，其阳性表达的强度存在着明显的差异。在WHO分级中Ⅲ-Ⅳ级脑星形细胞瘤MMPO的阳性表达为（76．52&#177;3．38）％，Fit-1为（72．90&#177;2．64）％，MVD为87．00&#177;4．18；Ⅰ-Ⅱ级MMP-9的阳性表达为（27．90&#177;2．53）％，Fit-1为（29．67&#177;2．87）％，MVD为48．62&#177;4．05。Ⅲ～Ⅳ级MMP-9、Flt-1和MVD的表达明显高于Ⅰ～Ⅱ级（P〈0．01）；三者的表达呈正相关。结论MMPO、Flt-1表达和MVD与脑星形细胞瘤的组织学类型及恶性程度相关，有可能做为判断肿瘤恶性程度及预后的辅助指标。     

Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma

To investigate the role of PTEN and matrix metalloproteinase-7 (MMP-7) expression in tumorigenesis and progression of gastric carcinoma, their expression in 113 gastric carcinomas was studied by immunohistochemistry. Microvessel density (MVD) was counted using the anti-CD34 antibody. The expressions of PTEN and MMP-7, and MVD were compared with the clinicopathological parameters of tumors, and the relationship between PTEN and MMP-7 expression and MVD was analyzed. It was found that PTEN was expressed less frequently in primary gastric carcinoma cells than in adjacent epithelial cells (P < 0.05), whereas this was reversed for MMP-7 (P < 0.05). PTEN expression was negatively correlated with invasion, metastasis, growth pattern, Lauren's classification and histological classification (P < 0.05). Matrix metalloproteinase-7 expression was positively associated with tumor size, Borrmann's classification, invasive depth, metastasis and TNM staging (P < 0.05), but negative with PTEN expression (P < 0.05). A positive correlation of MVD with tumor size, invasive depth, metastasis and TNM staging was found (P < 0.05). Microvessel density depended on decreased PTEN expression and increased MMP-7 expression (P < 0.05). The results of the present study suggested that down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma. Close correlation between PTEN on MMP-7 expression provided a novel insight into the regulatory effects of PTEN on MMP-7 expression in gastric carcinoma.     

MMP-9及TIMP-1在恶性外周神经鞘膜瘤中的表达及意义

目的探讨恶性外周神经鞘膜瘤(malignant peripheral nerve sheath tumours,MPNST)中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及组织金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的表达与病理分级、转移及预后的关系。方法采用免疫组化S-P法检测MPNST中MMP-9及TIMP-1表达。结果共检测了58例MPNST,其中MMP-9阳性表达率为89.7%(52/58),TIMP-1阳性表达率是60.3%(35/58)。MMP-9蛋白酶的表达与病理学分级、转移率呈正相关,与术后生存率呈负相关;而TIMP-1则相反。结论MMP-9、TIMP-1与MPNST病理学分级、转移及术后生存期有关,可作为判断恶性外周神经鞘膜瘤恶性程度及预后的可靠指标,为其治疗提供参考价值。     

Matrix metalloproteinases MMP-7, MMP-9 and their tissue inhibitor TIMP-1: expression in chronic sinusitis vs nasal polyposis

BACKGROUND: Nasal polyps (NP) are characterized by pseudocyst formation, whereas the mucosa in chronic sinusitis (CS) only shows a limited oedema. Matrix metalloproteinases (MMPs) are a family of endopeptidases able to degrade the extracellular matrix. Differences in histological features between CS and NP might be related to the respective expression of MMPs and their tissue inhibitors (TIMPs). OBJECTIVE: The aim of this study was to investigate MMP-7, MMP-9 and TIMP-1 proteins in NP and CS in comparison with normal mucosa. METHODS: Nasal samples, obtained from controls (n = 10), from NP (n = 8) and from CS (n = 10), were analysed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). RESULTS: In NP, compared with controls, staining for MMP-9 and MMP-7 appeared in blood vessels. Matrix metalloproteinase-9-positive inflammatory cells could be detected in increased numbers in pseudocyst formations. Concentrations of MMP-9 protein was found significantly increased in both CS and NP compared with controls, while MMP-7 was significantly increased in NP compared with controls and CS. Tissue inhibitors of metalloproteinase-1 protein was significantly increased in CS and NP when compared with controls. CONCLUSIONS: Chronic sinusitis and NP show different pattern of MMP-7/-9 and TIMP-1 expression. We suggest that this difference in regulation of enzymes is related to the respective tissue remodelling observed in both diseases.     

HL-60细胞ATRA诱导后MMP-9/TIMP-1表达的变化

为了检测HL-60细胞经过全反式维甲酸(ATRA)诱导后基质金属蛋白酶(MMP-9、MMP-2)及金属蛋白酶组织抑制剂1(TIMP-1)表达变化,并探讨其变化的意义。采用瑞氏染色观察细胞形态,WST1实验测定细胞增殖变化,NBT还原实验测定细胞分化状态,RT-PCR方法检测MMP-9、MMP-2、TIMP-1、VEGF的mRNA的表达。结果显示,HL-60细胞经ATRA作用24h后,随着细胞增殖降低与分化的发生,MMP-9mRNA表达增加,TIMP-1mRNA和VEGF表达降低,MMP-2mRNA未见明显表达。ATRA诱导HL-60细胞分化后MMP-9表达增加,而TIMP-1表达降低,MMP-9不促进HL-60细胞表达VEGF。     

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and thrombospondin-1 (TSP-1) expression in urothelial carcinomas

Angiogenesis is a multistep process that depends on the balance of proangiogenic factors and inhibitors as well as on interactions with the extracellular matrix. We examined the immunohistochemical expression of the defining angiogenic agents, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), and the antiangiogenic agent thrombospondin-1 (TSP-1) in 131 patients with urethelial carcinoma and correlated their expression levels with clinicopathological parameters. VEGF and MMP-9 expression was higher in high-grade tumors than in low-grade tumors (p=0.000 and p=0.001, respectively), whereas the reverse was true for TSP-1 (p=0.000). VEGF and MMP-9 expression was higher in deeper tumors compared to superficial tumors and in invasive tumors compared to non-invasive tumors (p=0.001 and p=0.001, respectively), while TSP-1 was lower (p=0.000). We could differentiate 22 of 41 muscle-invasive (T2) cases as superficial (T2a; n=7) or deep (T2b; n=15), but no difference was found between them regarding VEGF, MMP-9, or TSP-1 expression (p=0.783, p=0.289, and p=0.783, respectively). There was a positive correlation between VEGF and MMP-9 expression (p=0.008, r=0.23) but a negative correlation between MMP-9 and TSP-1 expression (p=0.014, r=-0.21). Increased VEGF and MMP-9 expression as well as decreased TSP-1 expression may play considerable roles in the invasion and differentiation of urothelial carcinoma.